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Life SciencesExperiments were performed in rat spinal cord cells in vivo and on hippocampal pyramidal cells in vitro. These investigations suggest that acute and chronic treatment...
Experiments were performed in rat spinal cord cells in vivo and on hippocampal pyramidal cells in vitro. These investigations suggest that acute and chronic treatment renders the neurons subsensitive to opiate alkaloids without altering their sensitivity to opioid peptides. The experiments performed in the dorsal horn of the spinal cord provide evidence that in this structure mu- and delta-receptors may also be localized on the same cell. The evidence for the existence of distinct types of opiate receptors as originally proposed by (1) and suggested by the differing pattern of opiate and opioid peptide activity in various assay systems has been substantiated by investigations involving the selective development of tolerance and the protection of a particular receptor subtype by chemical manipulation. Furthermore, they have been characterized by the use of low concentrations of radiolabelled agonists and antagonists and through the ability of GTP to influence differentially their binding to the opiate receptor (for refs. see: 2). Recently autoradiographic techniques were able to provide direct evidence by mu- and delta-receptors in the mammalian brain (3; 4; 5; 6; and cits. therein). The presence of multiple opiate receptors located on the same cell is suggested by the present study.
Topics: Animals; Brain; Electric Stimulation; Enkephalin, Methionine; Hippocampus; In Vitro Techniques; Male; Naloxone; Neurons; Rats; Rats, Inbred Strains; Receptors, Opioid; Spinal Cord
PubMed: 6298526
DOI: 10.1016/0024-3205(82)90152-7 -
Forensic Science International Aug 1998The universally accepted 300 ng/ml cut-off limit for opiate assays stated to be mandatory for all drug screening laboratories by the Substance Abuse and Mental Health...
The universally accepted 300 ng/ml cut-off limit for opiate assays stated to be mandatory for all drug screening laboratories by the Substance Abuse and Mental Health Services Administration, has been questioned recently due to positive results being obtained following the ingestion of poppy seed containing food products. To establish the plausibility of the 'the poppy seed defence' the concentrations of codeine, norcodeine, morphine, normorphine and thebaine (a potential marker for seed ingestion) in several varieties of poppy seeds from different countries were quantified by GC-MS. The country of origin of the seed specimen analysed and the preparation of the seeds prior to their culinary use was found to influence the alkaloid concentration determined. The maximum morphine and codeine concentrations determined in the seeds were found to be 33.2 and 13.7 micrograms/g seed respectively. In addition, thebaine concentrations were found to vary with each seed sample analysed. Following the consumption of bread rolls (mean 0.76 g seed covering per roll) by four subjects, all urine specimens analysed produced negative results (using the Dade Bebring EMIT II opiate screening assay) with the exception of one subject (body weight 63.0 kg) who consumed two poppy seed rolls. In this subject opiate positive screening results were obtained for up to 6 h post ingestion with maximum urinary morphine and codeine concentrations of 832.0 ng/ml (@ 2-4 h post ingestion) and 47.9 ng/ml (@ 0-2 h post ingestion) respectively being achieved. Following the ingestion of poppy seed cake containing an average of 4.69 g of seed per slice by four individuals, opiate positive screening results were obtained for up to 24 h. In one subject (dose equivalent to 0.07 g poppy seed/kg body weight) maximum urinary morphine and codeine concentrations of 302.1 ng/ml (@ 0-2 h) and 83.8 ng/ml (@ 2-4 h) respectively were recorded. The elimination of thebaine was found to vary widely between individuals, therefore suggesting that its absence from a specimen is not necessarily indicative of opiate abuse. These findings demonstrate that the poppy seed defence could be used as an argument in medico-legal and employment medical cases. Great care should therefore be taken when interpreting the data produced when screening for opiates.
Topics: Administration, Oral; Adult; Codeine; Food Analysis; Gas Chromatography-Mass Spectrometry; Humans; Male; Morphine; Morphine Derivatives; Narcotics; Papaver; Plants, Medicinal; Seeds; Thebaine
PubMed: 9800363
DOI: 10.1016/s0379-0738(98)00107-8 -
Journal of Analytical Toxicology Oct 1999Until recently, most laboratories used an opiate immunoassay screening and confirmation cutoff value of 300 ng/mL for codeine and morphine detection by gas...
Until recently, most laboratories used an opiate immunoassay screening and confirmation cutoff value of 300 ng/mL for codeine and morphine detection by gas chromatography-mass spectrometry (GC-MS). The cutoff value for opiates was increased to 2000 ng/mL or higher in various laboratories because of concerns that small doses of codeine and foods containing poppy seeds would give a positive opiate-screening result. Workplace drug-testing programs in the U.S. raised the opiate cutoff value to 2000 ng/mL on 30 November 1998. The objective of this study is to describe the results of opiate testing of 8600 urine specimens collected over 24 months with a 2000-ng/mL screening and confirmation (codeine and morphine) cutoff value. Specimens were screened by the EMITdau opiate assay using an in-house 2000-ng/mL morphine calibrator. Presumptive positive findings (N = 621) were analyzed quantitatively by GC-MS for codeine and morphine. One hundred and eighty six urine specimens were positive for codeine and morphine (> 2000 ng/mL), 298 specimens were positive for codeine only (> 2000 ng/mL) and 26 specimens were positive for morphine only (> 2000 ng/mL). All remaining specimens had codeine and morphine values < 2000 ng/mL. The codeine and morphine confirmation rate in this program reduced from 7.1% in 1994-1996 (300-ng/mL cutoff) to 2.1% in 1997-1998 with a 2000-ng/mL cutoff value. The codeine-only confirmation rate lowered from 6.6% (300-ng/mL cutoff) to 3.4% (2000-ng/mL cutoff). It was concluded that increasing opiate screening and codeine and morphine confirmation cutoff values led to > 300% reduction in the confirmed-positive rate for codeine and morphine and a 47% reduction in codeine-only confirmations in a urine drug-testing program where codeine was the major opiate used.
Topics: Codeine; Enzyme Multiplied Immunoassay Technique; Gas Chromatography-Mass Spectrometry; Humans; Morphine; Sensitivity and Specificity; Urine
PubMed: 10517566
DOI: 10.1093/jat/23.6.549 -
Critical Reviews in Toxicology Feb 2019The (ab)use of designer drugs and steroid hormones has gained popularity due to the lower chance of getting caught, as routine drug or doping tests may miss these... (Review)
Review
The (ab)use of designer drugs and steroid hormones has gained popularity due to the lower chance of getting caught, as routine drug or doping tests may miss these (novel) compounds. Current analytical approaches mostly make use of targeted, structure-based techniques, such as immunoassays or mass spectrometry (MS)-based methods. However, these approaches have limitations, including a lack of cross-reactivity and the need for prior knowledge of molecular identity. This has initiated considerable interest in the so-called "untargeted" screening strategies to detect these compounds. The use of "untargeted" MS-based screening methods (e.g. gas chromatography MS and especially high-resolution MS) has gained considerable interest to detect and identify novel compounds. However, due to their expensive and time-consuming character, very sophisticated analytical methods are not ideal as a first-line screening method and are not routinely implemented in most laboratories. Given the above, it is clear that there lies potential in novel "untargeted" screening approaches, which are less expensive, more high-throughput-amenable and more routinely applicable. Activity-based assays, capable of monitoring the biological activity of an abused substance in a biological matrix, have been proposed as an alternative. These biological assays do not require knowledge about a compound's structure and could be used as a first-line screening tool to identify potentially positive samples. In this review, we focus on activity-based reporter bioassays for the detection of steroids and drugs of abuse in biological matrices. As for drugs of abuse, only bioassays for detecting cannabinoid or opioid activity in biological matrices are available, only (synthetic) cannabinoid receptor agonists and opioids are discussed.
Topics: Biological Assay; Doping in Sports; Humans; Substance Abuse Detection
PubMed: 30919714
DOI: 10.1080/10408444.2019.1576588 -
Biochemical and Biophysical Research... Jul 1976
Topics: Amino Acid Sequence; Amino Acids; Animals; Binding Sites; Biological Assay; Brain; Cell Membrane; Dose-Response Relationship, Drug; Narcotics; Oligopeptides; Protein Binding; Rats
PubMed: 962912
DOI: 10.1016/0006-291x(76)90243-6 -
Journal of Analytical Toxicology May 2020A comparative analysis of enzyme-linked immunosorbent assay (ELISA) and quadrupole time-of-flight mass spectrometry (LC-QTOF) for the detection of opioids in blood...
A comparative analysis of enzyme-linked immunosorbent assay (ELISA) and quadrupole time-of-flight mass spectrometry (LC-QTOF) for the detection of opioids in blood samples is presented. The Orange County Crime Lab (OCCL) was concerned that the opioid drug class was not accurately detected at low concentrations due to the use of LC-QTOF as a non-targeted screening method for multiple classes of drugs. In order to investigate this issue, 968 ante-mortem and postmortem blood samples were analyzed by ELISA for the presence of the following opioids: morphine, morphine-glucuronide, codeine, codeine-glucuronide, hydrocodone, hydromorphone, hydromorphone-glucuronide, oxycodone, oxymorphone and oxymorphone-glucuronide. All samples had been previously analyzed by LC-QTOF. Overall, 84 samples tested positive for opioids. Discrepant samples between ELISA and LC-QTOF were analyzed by a liquid chromatography tandem mass spectrometry confirmation method in order to determine the true composition of the sample. Upon review of the discrepant samples, no forensically relevant concentration of opioids was missed by LC-QTOF. Thus, the ability of the OCCL's LC-QTOF screening method was verified to detect opioids at low concentrations.
Topics: Analgesics, Opioid; Chromatography, Liquid; Codeine; Enzyme-Linked Immunosorbent Assay; Humans; Hydrocodone; Hydromorphone; Morphine; Morphine Derivatives; Oxycodone; Oxymorphone; Substance Abuse Detection
PubMed: 31897469
DOI: 10.1093/jat/bkz109 -
Journal of Forensic and Legal Medicine Feb 2019Opium poppy has important medical, socioeconomic, forensic and political implications. More than 80 benzylisoquinoline alkaloids have been described, many of them with... (Review)
Review
Opium poppy has important medical, socioeconomic, forensic and political implications. More than 80 benzylisoquinoline alkaloids have been described, many of them with relevant therapeutic properties such as morphine, codeine, papaverine and noscapine. Heroin, a semi-synthetic drug produced from morphine is a worldwide serious cause of morbidity and mortality. Heroin dependence is complex phenomenon with environmental and genetic influence, and several biomarkers of exposure have been proposed. This work aims to review the metabolism and metabolomics of opiates with particular interest on their relevance as potential clinical and forensic antemortem and postmortem biomarkers. It is known that the heroin is mainly a prodrug that is rapidly deacetylated in blood to its active metabolite, 6-acetylmorphine, which is then subsequently slowly deacetylated to morphine. Therefore, 6-acetylmorphine has been used as the main target metabolite to prove heroin abuse in clinical, but mostly in forensic routine. Nevertheless, its applicability is limited due to the reduced detection window. Therefore, morphine (and its metabolites morphine-3-glucuronide and morphine-6-glucuronide), codeine, codeine-6-glucuronide, 6-acetylcodeine, noscapine (and its metabolites meconine, desmethylmeconine, and cotarnine), papaverine (and its metabolites 6-desmethylpapaverine, hydroxypapaverine, dihydroxypapaverine, 6-desmethylpapaverine-glucuronide) and thebaine (and acetylthebaol and the non-acetylated analog thebaol) have been additionally recommended to obtain the most reliable results possible. More recently, the identification by metabolomics analysis of several endogenous compounds offered an alternative approach of significant importance to uncover toxic effects. Profound alterations in the neurotransmitters levels and energy and amino acid metabolism have been reported with l-tryptophan, 5-hydroxytryptamine and 5-hydroxyindoleacetate being suggested as potential non-specific biomarkers of long-term heroin addiction. These endogenous metabolic profiles and exogenous components that together comprise the exposome will certainly help to uncover metabolic disturbances and patterns that may be associate to addiction with relevant clinical and forensic implications.
Topics: Analgesics, Opioid; Biomarkers; Codeine; Forensic Toxicology; Heroin; Humans; Metabolomics; Molecular Structure; Morphine; Opiate Alkaloids; Opioid-Related Disorders
PubMed: 30621882
DOI: 10.1016/j.jflm.2018.12.005 -
Journal of Applied Behavior Analysis Jul 2020Polydrug use is a common problem among patients in opioid-substitution treatment. Polydrug use has been reduced by administering abstinence-reinforcement contingencies...
Polydrug use is a common problem among patients in opioid-substitution treatment. Polydrug use has been reduced by administering abstinence-reinforcement contingencies in a sequence, such that a single drug is targeted until abstinence is achieved, and then an additional drug is targeted. The present study examined effects of administering abstinence-reinforcement contingencies sequentially based on time rather than on achieved abstinence. Participants accessed paid work (about $10/hr maximum) in the Therapeutic Workplace by providing urine samples 3 times per week. The urine samples were tested for opiates and cocaine. During an induction period, participants earned maximum pay independent of drug abstinence. Then, maximum pay depended upon urine samples that were negative for opiates. Two weeks later, maximum pay depended upon urine samples that were negative for both opiates and cocaine. Opiate and cocaine abstinence increased following administration of the respective contingencies. The time-based administration of abstinence reinforcement increased opiate and cocaine abstinence.
Topics: Cocaine; Cocaine-Related Disorders; Female; Humans; Male; Opiate Alkaloids; Opioid-Related Disorders; Reinforcement, Psychology; Time Factors
PubMed: 32249414
DOI: 10.1002/jaba.702 -
The Journal of Maternal-fetal &... Apr 2021Neonatal opiate withdrawal syndrome (NOWS), previously known as neonatal abstinence syndrome (NAS), is a growing public health concern as opiate misuse and...
Neonatal opiate withdrawal syndrome (NOWS), previously known as neonatal abstinence syndrome (NAS), is a growing public health concern as opiate misuse and opioid-related overdoses, from both prescription and illicit sources, continue to rise in the USA. As more than 90% of females abusing opioids are of child-bearing age, the failure to adequately address the opioid epidemic continues to negatively impact the next generations. Accurate and timely identification of infants at risk for withdrawal from exposure is critical to ensure high-quality perinatal and neonatal care. Beginning with an evaluation of current best practices and performing a literature review, we identify the challenges to current screening processes and how these limitations limit the ability to provide appropriate care to infants at the risk of withdrawal. We first describe the limitations of the available assays for the detection of opioid and opioid metabolites across different biological sources from both the mother and the infant. We then present a discussion surrounding factors that contribute to maternal willingness to disclose use. Particularly, in light of the limitations of biological screening, any barrier to maternal disclosure further complicates effective care delivery. Barriers to disclosure include legal ramifications and state policies, provider and societal behaviors and biases, and maternal factors. Moving forward, universal prenatal screening surveys coupled with enhanced outreach and education to providers centering on the limitations of both patient report and biological sampling, as well as comprehensive and supportive services for women of reproductive age with substance use disorders, are needed to both enhance detection for NOWS and improve long-term maternal-child health.
Topics: Analgesics, Opioid; Child; Female; Humans; Infant; Infant, Newborn; Neonatal Abstinence Syndrome; Opiate Alkaloids; Opiate Substitution Treatment; Opioid-Related Disorders; Perinatal Care; Pregnancy; Pregnancy Complications
PubMed: 31195865
DOI: 10.1080/14767058.2019.1627316 -
International Anesthesiology Clinics 1986Spinal opiate analgesia has opened an exciting new field of research and has also rapidly gained widespread clinical acceptance. This mode of administration has obvious... (Comparative Study)
Comparative Study Review
Spinal opiate analgesia has opened an exciting new field of research and has also rapidly gained widespread clinical acceptance. This mode of administration has obvious and definite advantages over conventional pain therapy; however, the field is still at an early stage of development. More research is clearly needed to provide methods for coping with some of the drawbacks of this method of pain relief. Important areas for future research include (1) the CSF kinetics of opiates; (2) the physiological mechanisms underlying the rostral spread of drugs within the CSF compartment; (3) a search for safer and more selective drugs; and (4) an evaluation of the extent to which pain-modulating systems at different levels in the CNS can be regulated by opiates and drugs interfering with other neurotransmitters. In this context it is essential to emphasize the importance of simultaneous study of the pharmacokinetics and the pharmacodynamic/clinical effects in providing a rational basis for a better understanding of the mechanisms of actions underlying spinal opiate analgesia.
Topics: Anesthesia, Epidural; Biological Availability; Dose-Response Relationship, Drug; Half-Life; Humans; Injections, Spinal; Kinetics; Morphine
PubMed: 3519470
DOI: 10.1097/00004311-198602420-00005