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Hair Morphine Concentrations of Fatal Heroin Overdose Cases and Living Heroin Users
Abstract
To compare heroin and other opiate use of heroin overdose fatalities, current street heroin users and drug-free therapeutic community clients.
Hair morphine concentrations that assess heroin use and other opiate use in the 2 months preceding interview or death were compared between heroin overdose fatalities diagnosed by forensic pathologists (FOD) (n = 42), current street heroin users (CU) (n = 100) and presumably abstinent heroin users in a drug-free therapeutic community (TC) (n = 50).
Sydney, Australia.
The mean age and gender breakdown of the three samples were 32.3 years, 83% male (FOD), 28.7 years, 58% male (CU) and 28.6 years, 60% male (TC). The median blood morphine concentration among the FOD cases was 0.35 mg/l, and 82% also had other drugs detected. There were large differences between the three groups in hair morphine concentrations, with the CU group (2.10 ng/mg) having concentration approximately four times that of the FOD group (0.53 ng/mg), which in turn had a concentration approximately six times that of the TC group (0.09 ng/mg). There were no significant differences between males and females in hair concentrations within any of the groups. Hair morphine concentrations were correlated significantly with blood morphine concentrations among FOD cases (r = 0.54), and self-reported heroin use among living participants (r = 0.57).
The results indicate that fatal cases had a lower degree of chronic opiate intake than the active street users, but they were not abstinent during this period.
... Subjective estimates can be obtained by interviewing living addicts, but the reliability in self-reports may be questioned. However, hair analysis can provide objective data about previous drug use and disclose periods of abstinence [74,75,86]. ...
... The existence of different types of melanin including eumelanins (black-brown) and pheomelanins (yellow-red) complicates such comparisons even further [115]. [74,75,86]. All concluded that absence or low concentrations of opiates in hair was due to abstinence and hence may have been the cause of death owing to reduced tolerance. ...
... Most of the samples analyzed have been 1-4 cm long, and hence the relative contribution from a recent exposure to the positive result is impossible to establish. Both Tagliaro [75] and Darke [86] used hair samples of considerable length when concluding that deceased heroin addicts had lower levels of morphine in hair than living abusers. Thus from such data, it can only be concluded that the average levels in hair were lower among the deceased overdose subjects, since the hair analysis was not accurate enough to tell if subjects recently had been using opiates or not. ...
... Another counter-intuitive nding in the epidemiology of overdose is that at autopsy a large proportion of overdose fatalities have relatively low blood morphine concentrations (heroin is rapidly metabolised into morphine once administered). 42 This con icts with the widely accepted view that a fatal heroin "overdose" is the result of using a quantity or quality (purity) of heroin in excess of the person's current tolerance to the drug. If this were the case, one might expect to nd relatively high blood levels of morphine at autopsy in people with a long history of opioid dependence. ...
... 53 A recent Italian study 54 found that morphine concentrations in the hair samples of fatal overdose cases were signi cantly lower than those of current users. This nding was recently supported by Darke et al. 42 in a replication of this study among Sydney heroin overdose fatalities. The conclusion of both these research groups was that fatal heroin overdose cases were using considerably less heroin in the months preceding death than were active street users, suggesting that loss of opioid tolerance in this group is at least partially responsible for their fatal overdose. ...
... It has been suggested that after a decade or more of heroin use users may cut down their consumption as they tire of the rigours of the heroin-using life-style. 42 Pharmacological mechanisms of tolerance Variation has been found in the acquisition of tolerance to different effects of opiates. Tolerance to the respiratory depressant effects of opioids may be incomplete and may develop more slowly than tolerance to the euphoric effects. ...
Over the past decade fatal opioid overdose has emerged as a major public health issue internationally. This paper examines the risk factors for overdose from a biomedical perspective. While significant risk factors for opioid overdose fatality are well recognized, the mechanism of fatal overdose remains unclear. Losses of tolerance and concomitant use of alcohol and other CNS depressants clearly play a major role in fatality; howeve, such risk factors do not account for the strong age and gender patterns observed consistently among victims of overdose. There is evidence that systemic disease may be more prevalent in users at greatest risk of overdose. We hypothesize that pulmonary and hepatic dysfunction resulting from such disease may increase susceptibility to both fatal and non-fatal overdose. Sequelae of non-fatal overdose are recognized in the clinical literature but few epidemiological data exist describing the burden of morbidity arising from such sequelae. The potential for overdose to cause persisting morbidity is reviewed.
... Another counter-intuitive nding in the epidemiology of overdose is that at autopsy a large proportion of overdose fatalities have relatively low blood morphine concentrations (heroin is rapidly metabolised into morphine once administered). 42 This con icts with the widely accepted view that a fatal heroin "overdose" is the result of using a quantity or quality (purity) of heroin in excess of the person's current tolerance to the drug. If this were the case, one might expect to nd relatively high blood levels of morphine at autopsy in people with a long history of opioid dependence. ...
... 53 A recent Italian study 54 found that morphine concentrations in the hair samples of fatal overdose cases were signi cantly lower than those of current users. This nding was recently supported by Darke et al. 42 in a replication of this study among Sydney heroin overdose fatalities. The conclusion of both these research groups was that fatal heroin overdose cases were using considerably less heroin in the months preceding death than were active street users, suggesting that loss of opioid tolerance in this group is at least partially responsible for their fatal overdose. ...
... It has been suggested that after a decade or more of heroin use users may cut down their consumption as they tire of the rigours of the heroin-using life-style. 42 Pharmacological mechanisms of tolerance Variation has been found in the acquisition of tolerance to different effects of opiates. Tolerance to the respiratory depressant effects of opioids may be incomplete and may develop more slowly than tolerance to the euphoric effects. ...
Over the past decade fatal opioid overdose has emerged as a major public health issue internationally. This paper examines the risk factors for overdose from a biomedical perspective. While significant risk factors for opioid overdose fatality are well recognized, the mechanism of fatal overdose remains unclear. Losses of tolerance and concomitant use of alcohol and other CNS depressants clearly play a major role in fatality; however, such risk factors do not account for the strong age and gender patterns observed consistently among victims of overdose. There is evidence that systemic disease may be more prevalent in users at greatest risk of overdose. We hypothesize that pulmonary and hepatic dysfunction resulting from such disease may increase susceptibility to both fatal and non-fatal overdose. Sequelae of non-fatal overdose are recognized in the clinical literature but few epidemiological data exist describing the burden of morbidity arising from such sequelae. The potential for overdose to cause persisting morbidity is reviewed.
... However a larger study that examined hair collected from subjects participating in a controlled heroinmaintenance program by Kintz, Bundeli, Brenneisen, and Ludes (1998) demonstrated that using quantitative drug measurements in hair to determine the amount of drug ingested was not applicable due to the large degree of observed sample variability. Other studies have suggested using hair to monitor for determination of drug use, tolerance, and abstinence, as well as the establishment of the type of drug use, rather than trying to correlate the amount of drug ingested to drug concentrations found in hair (Valente, Cassini, Pigliapochi, & Vansetti, 1981;Tagliaro, De Battisti, Smith, & Marigo, 1998;Darke, Hall, Kaye, Ross, & Duflour, 2002;Kugelberg et al., 2007). ...
... Heroin is quickly deacetylated to 6-monoacetylmorphine (6-MAM) and morphine in the body and the presence of 6-MAM in biological fluids and hair is required to distinguish between heroin and morphine administration (Society of Hair Testing, 2004). Because of the short half-life of heroin and its metabolites in blood and urine, hair is a better matrix to analyse when attempting to establish a history of drug use or abuse, i.e. previous administration of heroin, as drug and drug metabolites can be detected in hair long after drug exposure (Polettini, Stramesi, Vignali, & Montagna, 1997;Girod & Staub, 2001;Darke et al., 2002;Jones, Tomlinson, & Moore, 2002;Druid et al., 2007;Kronstrand et al., 2007). The major metabolites of heroin, namely morphine and 6-MAM, have been positively identified in hair of known addicts (Girod & Staub, 2001). ...
... mg/l). To conclude the history of drug abuse (Darke et al., 2002;Tagliaro et al., 1998) morphine were detected in hair specimens 2.96 AE 0.42 ng/mg (range 0.8-8.6 ng/mg). Alcohol was detected in 58% (n = 11) of all cases; median ethanol concentration was 1.05 AE 0.27% (range 0.3-3.9%). ...
... We cannot judge with certainty whether the observed changes in brain tissue were caused by a lethal drug overdose or by a longterm drug exposure during the preceding life of subjects. In the present study, chronical opiate usage was confirmed the presence of morphine in all hair specimens suggesting that the observed changes are due to chronical (at least, half-year-long) opiate intoxication rather than acute disturbances due to heroin overdose (Darke et al., 2002;Tagliaro et al., 1998). Furthermore, taking into consideration that the expression of iNOS takes few hours (Heneka and Feinstein, 2001), while acute lethal intoxication requires less than an hour (Vhite and Irvine, 1999), we believe that the changes resulted from chronic opiate effects (and, perhaps, from previous episodes of abstinent syndrome). ...
In order to determine the role of inducible nitric oxide synthase (iNOS) and tumor necrosis factor-alpha (TNF-alpha) in the pathogenesis of opiate addiction in humans, the expression of both was analyzed in the locus coeruleus (LC) of patients who died from heroin overdose. In control subjects, NADPH-diaphorase (NADPHd) histochemistry was mainly observed in non-noradrenerdic neurons, some glial and endothelial cells. However, in the brain of opiate addicts, NADPHd and iNOS expression was detected in noradrenergic LC cells, correlating with an increase in iNOS and TNF-alpha expression in glial cells as revealed by immunohistochemical and Western blot analyses. These findings indicate that sustained overproduction of cytokine and NO via iNOS expression may be responsible, at least in part, for some neurochemical changes in the locus coeruleus caused by chronic opiate usage in humans.
... The risk of overdose has been found to be higher in patients experiencing withdrawal symptoms (Coffin et al., 2007) and is significantly increased for those who recommence using opioids after abstinence/loss of tolerance (Gossop et al., 1996;Neira-Leon et al., 2006;Oliver and Keen, 2003;Tagliaro et al., 1998;Thiblin et al., 2004). Other studies however contradict this and describe results where overdose is associated with less recent heroin or polydrug use rather than with abstinence (Darke et al., 2002;Druid et al., 2007). In most cohort studies, overdose is the principal or one of the principal causes of death among drug users, ranging from 14% to 47% of reported deaths (Brugal et al., 2005;Dolan et al., 2005;Perucci et al., 1991;Roy et al., 2004;van Ameijden et al., 1999). ...
... Interestingly, Darke and al. (2002) when comparing chronic opioid intake through hair analysis in individuals who died from overdose and street living heroin users, found that intake was lower in the former group. This observation suggests that selfmanagement of withdrawal symptoms through heroin intake in individuals who have lost some tolerance (as in the case of exposure to low dosage substitution treatment) may increase the risk of overdose. ...
Even in the highly active antiretroviral therapy (HAART) era, individuals HIV-infected through injecting drug use (IDUs) are at increased risk of death due to the burden of competing events such as liver disease, overdose and suicide. The objective of this study was to explore the role which life events' experience, in particular drug-related events such as detoxification or withdrawal symptoms, may play on the risk of death in HIV-infected IDUs. Our analysis was based on longitudinal data of 296 HIV-infected IDUs from when they started HAART. Data collection included medical records and patient's self-reports detailing, among other information, life events including drug-related problems. Multiple imputations for missing data in the explanatory variables together with Cox models were used to identify predictors of death. During HAART follow-up, 26 deaths occurred, corresponding to 1.8 deaths per 100 person-years. The majority (N=8) were attributable to liver disease while 5 were from unknown causes (found deceased at home or in a car). After adjustment for age and time-dependent viral load (>10,000 cp/ml) individuals experiencing withdrawal symptoms had a fivefold increased risk of death with respect to the others. Withdrawal symptoms in IDUs living with HIV reflect physicians' difficulties in managing their patients' opioid dependence. Early detection and increasing substitution dosages or switching to a more adequate treatment could prevent possible drug-related deaths.
... Empirical evidence for reduced tolerance as a risk factor comes from post-mortem analyses, showing heroin overdose victims had lower morphine concentrations in the hair and blood than currently living heroin users (Darke et al., 2002). Loss of tolerance makes clients leaving drug-free rehab particularly prone to fatal overdose. ...
... This makes sense in terms of the tolerance-overdose model since we know that tolerance rapidly decreases with abstinence (White et al., 1999 a). However in many study samples, the majority of HODs occur in older (male) long-term addicts who otherwise might be expected to have a high tolerance, with fatal cases often revealing relatively low blood morphine concentrations (Darke et al., 2002; WarnerSmith et al., 2002). Medical examinations of addict HOD deaths often reveal blood morphine levels similar to those of addicts who died from other causes such as homicide (Warner-Smith et al., 2002). ...
Heroin overdose, more accurately termed 'heroin-related overdose' due to the frequent involvement of other drugs, is the leading cause of mortality among regular heroin users. (Degenhardt et al., 2010) Heroin injectors are at greater risk of hospital admission for heroin-related overdose (HOD) in the eastern United States where Colombian-sourced powder heroin is sold than in the western US where black 'tar' heroin predominates. (Unick et al., 2014) This paper examines under-researched influences on HOD, both fatal and non-fatal, using data from a qualitative study of injecting drug users of black tar heroin in San Francisco and powder heroin in Philadelphia Data were collected through in-depth, semi-structured interviews carried out in 2012 that were conducted against a background of longer-term participant-observation, ethnographic studies of drug users and dealers in Philadelphia (2007-12) and of users in San Francisco (1994-2007, 2012). Our findings suggest three types of previously unconsidered influences on overdose risk that arise both from structural socio-economic factors and from the physical properties of the heroin source-types: 1) retail market structure including information flow between users; 2) marketing techniques such as branding, free samples and pricing and 3) differences in the physical characteristics of the two major heroin source forms and how they affect injecting techniques and vascular health. Although chosen for their contrasting source-forms, we found that the two cities have contrasting dominant models of drug retailing: San Francisco respondents tended to buy through private dealers and Philadelphia respondents frequented an open-air street market where heroin is branded and free samples are distributed, although each city included both types of drug sales. These market structures and marketing techniques shape the availability of information regarding heroin potency and its dissemination among users who tend to seek out the strongest heroin available on a given day. The physical characteristics of these two source-types, the way they are prepared for injecting and their effects on vein health also differ markedly. The purpose of this paper is to examine some of the unexplored factors that may lead to heroin-related overdose in the United States and to generate hypotheses for further study.
Copyright © 2015 Elsevier Ltd. All rights reserved.
... It has been suggested that tolerance to respiratory depression is less pronounced than to other effects such as euphoria (White and Irvine, 1999). Surprisingly, levels of heroin and its metabolites in overdose victims are often lower than that expected in highly tolerant individuals (Darke et al, 2002). This has been interpreted as the victims having taken their normal dose of heroin during a period of reduced tolerance, such as that occurring after incarceration or detoxification, with the drug then inducing greater respiratory depression than expected (White and Irvine, 1999). ...
Opioids are the most common drugs associated with unintentional drug overdose. Death results from respiratory depression. Prolonged use of opioids results in the development of tolerance but the degree of tolerance is thought to vary between different effects of the drugs. Many opioid addicts regularly consume alcohol (ethanol) and post-mortem analyses of opioid overdose deaths have revealed an inverse correlation between blood morphine and ethanol levels. In the present study we determined whether ethanol reduced tolerance to the respiratory depressant effects of opioids. Mice were treated with opioids (morphine, methadone or buprenorphine) for up to 6 days. Respiration was measured in freely moving animals breathing 5% CO2 in air in plethysmograph chambers. Antinociception (analgesia) was measured as the latency to remove the tail from a thermal stimulus. Opioid tolerance was assessed by measuring the response to a challenge dose of morphine (10 mg/kg i.p.). Tolerance developed to the respiratory depressant effect of morphine but at a slower rate than tolerance to its antinociceptive effect. A low dose of ethanol (0.3 mg/kg) alone did not depress respiration but in prolonged morphine treated animals respiratory depression was observed when ethanol was co-administered with the morphine challenge. Ethanol did not alter the brain levels of morphine. In contrast, in methadone or buprenorphine treated animals no respiratory depression was observed when ethanol was co-administered along with the morphine challenge. As heroin is converted to morphine in man selective reversal of morphine tolerance by ethanol may be a contributory factor in heroin overdose deaths.Neuropsychopharmacology accepted article preview online, 14 July 2015. doi:10.1038/npp.2015.201.
... 5 Two recent intriguing studies of heroin overdose fatalities examined the morphine content of hair, which is a measure of the average use of heroin use over the last few weeks. 18,19 Levels of morphine in the hair of fatal overdoses were much closer to those in a control group of abstinent former opiate users than to those of regular users, confirming that recent abstinence and low tolerance are related to death from heroin overdose. ...
... While morphine is a potent analgesic [33], and represses the central nervous system [34], methamphetamine is a psychostimulant [35]. In humans, it immediately induces an increase in metabolism and the release of 'pleasure' neurotransmitters [18]. ...
The larvae of necrophagous fly species are used as forensic tools for the determination of the minimum postmortem interval (PMI). However, any ingested drugs in corpses may affect larval development, thus leading to incorrect estimates of the period of infestation. This study investigated the effects of methamphetamine and its metabolite, p-hydroxymethamphetamine, on the forensically important Australian blowfly Calliphora stygia. It was found that the presence of the drugs significantly accelerated larval growth and increased the size of all life stages. Furthermore, drug-exposed samples remained as pupae for up to 78h longer than controls. These findings suggest that estimates of the minimum PMI of methamphetamine-dosed corpses could be incorrect if the altered growth of C. stygia is not considered. Different temperatures, drug concentrations and substrate types are also likely to affect the development of this blowfly. Pending further research, the application of C. stygia to the entomological analysis of methamphetamine-related fatalities should be appropriately qualified.
... [1] In forensic toxicology, the use of hair analysis in drug overdose deaths has been extensively investigated. [2][3][4][5][6] More recently, the monitoring of abstinence when re-granting a driving licence has made use of hair as the biological matrix of choice in some countries. [7][8][9][10][11][12] Typically, several hair samples are taken during the observation period and subjected to segmental analysis. ...
A sensitive and robust ultra high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method was developed and validated for quantification of amphetamine, methamphetamine, 3,4-methylenedioxyamphetamine and 3,4-methylenedioxy methamphetamine in hair samples. Segmented hair (10 mg) was incubated in 2M sodium hydroxide (80°C, 10 min) before liquid-liquid extraction with isooctane followed by centrifugation and evaporation of the organic phase to dryness. The residue was reconstituted in methanol:formate buffer pH 3 (20:80). The total run time was 4 min and after optimization of UHPLC-MS/MS-parameters validation included selectivity, matrix effects, recovery, process efficiency, calibration model and range, lower limit of quantification, precision and bias. The calibration curve ranged from 0.02 to 12.5 ng/mg, and the recovery was between 62 and 83%. During validation the bias was less than ±7% and the imprecision was less than 5% for all analytes. In routine analysis, fortified control samples demonstrated an imprecision <13% and control samples made from authentic hair demonstrated an imprecision <26%. The method was applied to samples from a controlled study of amphetamine intake as well as forensic hair samples previously analyzed with an ultra high performance liquid chromatography time of flight mass spectrometry (UHPLC-TOF-MS) screening method. The proposed method was suitable for quantification of these drugs in forensic cases including violent crimes, autopsy cases, drug testing and re-granting of driving licences. This study also demonstrated that if hair samples are divided into several short segments, the time point for intake of a small dose of amphetamine can be estimated, which might be useful when drug facilitated crimes are investigated. Copyright © 2014 John Wiley & Sons, Ltd.
... As with other opioids, the methadone blood concentration is highly variable in fatal cases, and there is an appreciable overlap between methadone blood concentrations found in drug addicts, who died of a methadone poisoning (0.06–3.10 mg/L, median = 0.28 mg/L, N = 59), and the concentration found in living subjects receiving methadone treatment (0.03–0.56 mg/L, median = 0.11 mg/L, N = 62) (Worm et al., 1993 ). Even though, different studies have been performed to investigate the risk factors of fatal outcome in opioid-related death, the background is still unclear (Buchard et al., 2010; Darke et al., 2002; Druid et al., 2007; Fugelstad et al., 2003; Tagliaro et al., 1998). Variations in methadone tolerance, the distribution and the rate of metabolism due to genetic factors could explain some of the differential sensitivity to overdose (White and Irvine, 1999). ...
... I. Demaret (1), a. Lemaître (2) m. ansseau (3) L'HÉROÏNE intRoduction Après la définition pharmacologique de l'héroïne, nous abordons l'historique de cette substance, ses effets, dont l'assuétude et les traitements de celle-ci, le lien entre consommation d'héroïne et délinquance et, enfin, son épidémiologie. Nous reprenons, à titre d'illustration, des données descriptives sur les 74 patients du projet TADAM, un projet pilote de traitement assisté par héroïne. ...
Heroin (or diacetylmorphine), a depressant nervous central system, is a semi-synthetic opiate. Its main adverse effect, respiratory depression, can lead to death, especially after an intravenous injection. By loss of tolerance, an overdose can be lethal following heroin use after a period of abstinence (voluntary or not). Mortality rate among heroin users is between 1 and 3%. Addiction, following a regular and continuous use, occurs in less than a quarter of persons who ever tried heroine. Heroin addicts often present with different problems (for instance, a criminal behaviour), without any obvious link with addiction. For a fraction of the addicts, addiction becomes a chronic relapsing disease, requiring a long term maintenance substitution therapy. However, relapses and sometimes continuous heroin use are frequent, For treatment resistant and severe heroin addicts, heroin-assisted treatment can be a solution. Despite the numerous available therapies, heroin is considered to be the drug with the most negative effects on the user.
... 27). Furthermore, in a significant proportion of deaths, the levels of opioids detected at autopsy were reported to be below the predicted fatal range for highly tolerant individuals, suggesting that opioid consumption was equal to or lower than that in living active heroin users (Tagliaro et al., 1998;Darke et al., 2002;Hickman et al., 2007). This finding suggests that some overdose deaths may be due to multiple drug toxicity and that the combination of ethanol and heroin or another opioid may pose a significant risk (Darke and Zador, 1996;Darke and Hall, 2003). ...
Consumption of ethanol is a considerable risk factor leading to deaths in heroin overdose. We have sought to determine whether a mildly intoxicating concentration of ethanol could alter morphine tolerance at the cellular level. In rat locus coeruleus (LC) neurons tolerance to morphine was reversed by acute exposure of the brain slice to ethanol (20 mM). Tolerance to the opioid peptide [D-Ala(2),N-MePhe(4),Gly-ol]-enkephalin (DAMGO) was not reversed by ethanol. Previous studies in LC neurons have revealed a role for PKCα in μ-opioid receptor (MOPr) desensitization by morphine and in the induction and maintenance of morphine tolerance but we have been unable to demonstrate that 20 mM ethanol produces significant inhibition of PKCα. The ability of ethanol to reverse cellular tolerance to morphine in LC neurons was absent in the presence of the phosphatase inhibitor, okadaic acid, indicating that dephosphorylation is involved. In HEK293 cells expressing MOPr ethanol reduced the level of MOPr phosphorylation induced by morphine. Ethanol reversal of tolerance did not appear to result from a direct effect on MOPr since acute exposure to ethanol (20 mM) did not modify the affinity of binding of morphine to the MOPr or the efficacy of morphine for G-protein activation as measured by [(35S)]-GTPγS binding. Similarly, ethanol did not affect MOPr trafficking. We conclude that acute exposure to ethanol enhances the effects of morphine by reversing the processes underlying morphine cellular tolerance.
... In addition to the trend for ethanol concentration to have an inverse relationship to the morphine concentration, the morphine concentrations themselves were often found to be lower than would have typically been predicted to be lethal given the level of opioid consumption in these highly tolerant individuals. The levels of opioid detected postmortem were found to be equal to or lower than the levels found in living active heroin users (Tagliaro et al., 1998;Darke et al., 2002;Hickman et al., 2007). These findings indicate that there may be a drug interaction responsible for the increased risk of overdose at lower opioid levels, and that the interaction between ethanol and opioids may be the main drug interaction responsible for these cases of polydrug overdose (Darke and Zador, 1996;Darke and Hall, 2003). ...
The chronic use of opioids in humans, accompanied by the development of tolerance, is a dangerous phenomenon in its own right. However chronic opioid use is often made more dangerous by the co-consumption of other substances. It has been observed that the blood level of opioids in postmortem analyses of addicts, who consumed ethanol along with the opioid, was much less than that observed in individuals that died from opioids alone. This relationship between ethanol and opioids led us to investigate the hypothesis that ethanol alters tolerance to opioids. In the present study, we report that ethanol significantly and dose-dependently reduced the antinociceptive tolerance produced by morphine and the cross tolerance between DAMGO and morphine in the mouse tail-flick test. The reversal of morphine tolerance was partially blocked by both the GABAA receptor blocker bicuculline and by the GABAB receptor blocker phaclofen and the administration of both inhibitors completely reversed the effects of ethanol on morphine tolerance. Diazepam, like ethanol, decreased morphine tolerance. However, this inhibition was reversed by the GABAA antagonist bicuculline but not by the GABAB antagonist phaclofen. These findings have important implications for individuals who abuse opioids and ethanol as well as suggest a mechanism to reduce the amount of opioid needed in chronic pain treatment.
... Tanaka (2002) reported a substantial increase in fatalities among humans when alcohol was ingested with a benzodiazepine, despite the relatively wide therapeutic index of benzodiazepines. Darke et al. (2002) found that among 42 deaths from heroin overdose, postmortem tests revealed that substances other than morphine were detected in over 80% of the cases. 2 The risk of overdose is increased when the user repeats administration of the drug. ...
To determine the acute lethal toxicity of a range of psychoactive substances in terms of the dose customarily used as a single substance for non-medical purposes.
A structured English-language literature search was conducted to identify experimental studies and clinical reports that documented human and non-human lethal doses of 20 abused substances that are distributed widely in Europe and North America. Four inclusion criteria were specified for the reports, and approximately 3000 relevant records were retrieved from search engines at Biosis, Science Citation Index, Google and the National Library of Medicine's Gateway. In order to account for different drug potencies, a 'safety ratio' was computed for each substance by comparing its reported acute lethal dose with the dose most commonly used for non-medical purposes.
The majority of published reports of acute lethal toxicity indicate that the decedent used a co-intoxicant (most often alcohol). The calculated safety ratios varied between substances by more than a factor of 100. Intravenous heroin appeared to have the greatest direct physiological toxicity; several hallucinogens appeared to have the least direct physiological toxicity.
Despite residual uncertainties, the substantial difference in safety ratios suggests that abused substances can be rank-ordered on the basis of their potential acute lethality.
A 32-year-old male was found dead on the couch in his flat. Several pieces of paraphernalia for the use of illicit drugs were located on the table in front of his body. The occasional consumption of heroin and cannabis products was known. Toxicological analyses of blood, urine, and of his long (88 cm) dreadlocks were performed after autopsy. General, unknown screenings of femoral vein blood and urine were performed using different extractions, gas chromatography/mass spectrometry (GC/MS) or high-performance liquid chromatography-diode array detection. A possible influence by alcohol was determined by gas chromatography/flame ionisation detection and an alcohol dehydrogenase method. The dreadlocks were washed, segmented in 83 parts (each ~1 cm length) and pulverised using a pebble mill. Quantitative determination of illicit drugs was performed using GC/MS (selected ion monitoring). Investigation of the femoral vein blood resulted in the detection of morphine (71.1 µg/L), 6-acetylmorphine (7.4 µg/L), and codeine (9.8 µg/L). These substances and 11-nor-9-carboxy-Δ9-tetrahydrocannabinol were also detected in urine. Alcohol concentrations in blood and urine were 2.31 and 3.01 ‰, respectively. Investigation of the segmental dreadlocks revealed concentration profiles for Δ9-tetrahydrocannabinol (≤0.65 µg/g), heroin (≤0.44 µg/g), morphine (≤1.02 µg/g), 6-acetylmorphine (≤1.13 µg/g), and codeine (≤0.32 µg/g). Strong correlations among morphine, 6-acetylmorphine, and codeine have been observed in the twelve most proximal hair segments. The consumption of heroin increased clearly in this time period. In summary, a discontinuous, long-term, illicit drug abuse and fatal intoxication with heroin and alcohol was verified by the analysis of these very long dreadlocks. © 2016 Japanese Association of Forensic Toxicology and Springer Japan
The unprecedented increase in unintentional overdose events that has occurred in tandem with escalating sales of prescription opioids over the past 2 decades has raised concerns about whether the therapeutic use of opioids has contributed to increases in overdose injury. Few controlled studies have examined the extent to which ecologic measures of increases in opioid prescribing and overdose injuries reflect risk among patients prescribed opioids, let alone whether some opioid regimens are safer than others.
To examine whether the risk of unintentional overdose injury is associated with the duration of opioid action (ie, long-acting vs short-acting formulations).
A propensity score-adjusted cohort study was conducted using population-based health care utilization data from the Veterans Administration Healthcare System. The patients were veterans with chronic painful conditions who began therapy with opioid analgesics between January 1, 2000, and December 31, 2009.
Unintentional overdoses that are explicitly coded using International Classification of Disease, Ninth Revision codes as drug or medication poisonings of accidental intent (E850.x-860.x) or undetermined intent (E980.x or drug poisoning [960.x-980.x] without an accompanying external cause of injury code).
A total of 319 unintentional overdose events were observed. Patients initiating therapy with long-acting opioids were more than twice as likely to overdose compared with persons initiating therapy with short-acting opioids. After adjustment for age, sex, opioid dose, and other clinical characteristics, patients receiving long-acting opioids had a significantly higher rate of overdose injury than did those receiving short-acting opioids (hazard ratio [HR], 2.33; 95% CI, 1.26-4.32). The risk associated with long-acting agents was particularly marked during the first 2 weeks after initiation of treatment (HR, 5.25; 1.88-14.72).
To our knowledge, the findings of the present study provide the first evidence that the risk of unintentional overdose injury is related to the prescribed opioid's duration of action. If replicated in other cohorts, our findings suggest that clinicians weighing the benefits and risks of initiating different opioid regimens should consider not only the daily dose prescribed but also the duration of opioid action, favoring short-acting agents whenever possible, especially during the first 2 weeks of therapy.
In Denmark, fatal poisoning among drug addicts is often related to methadone. The primary mechanism contributing to fatal methadone overdose is respiratory depression. Concurrent use of other central nervous system (CNS) depressants is suggested to heighten the potential for fatal methadone toxicity. Reduced tolerance due to a short-time abstinence period is also proposed to determine a risk for fatal overdose. The primary aims of this study were to investigate if concurrent use of CNS depressants or reduced tolerance were significant risk factors in methadone-related fatalities using segmental hair analysis. The study included 99 methadone-related fatalities collected in Denmark from 2008 to 2011, where both blood and hair were available. The cases were divided into three subgroups based on the cause of death; methadone poisoning (N = 64), poly-drug poisoning (N = 28) or methadone poisoning combined with fatal diseases (N = 7). No significant differences between methadone concentrations in the subgroups were obtained in both blood and hair. The methadone blood concentrations were highly variable (0.015–5.3, median: 0.52 mg/kg) and mainly within the concentration range detected in living methadone users. In hair, methadone was detected in 97 fatalities with concentrations ranging from 0.061 to 211 ng/mg (median: 11 ng/mg). In the remaining two cases, methadone was detected in blood but absent in hair specimens, suggesting that these two subjects were methadone-naive users. Extensive poly-drug use was observed in all three subgroups, both recently and within the last months prior to death. Especially, concurrent use of multiple benzodiazepines was prevalent among the deceased followed by the abuse of morphine, codeine, amphetamine, cannabis, cocaine and ethanol. By including quantitative segmental hair analysis, additional information on poly-drug use was obtained. Especially, 6-acetylmorphine was detected more frequently in hair specimens, indicating that regular abuse of heroin was common among the deceased. In conclusion, continuous exposure of methadone provide by segmental hair analysis suggested that reduced tolerance of methadone was not a critical factor among methadone-related fatalities. In contrast, a high abundance of co-ingested CNS depressants suggested that adverse effects from drug-drug interactions were more important risk factors for fatal outcome in these deaths.
Background
Overdose is a major cause of morbidity and mortality amongst opioid users. This paper reported on recent non-fatal overdose amongst the Australian Treatment Outcome Study (ATOS) cohort at 11 year follow-up, and characteristics that predict recent overdose. Methods: Longitudinal cohort. 431 (70.1%) of the original 615 participants were interviewed. Participants were administered the ATOS structured interview, addressing demographics, treatment history, drug use, heroin overdose, criminality, health and psychopathology. Findings: Mean time since heroin initiation was 20.4 yrs. By 11 year follow-up, the proportion who had overdosed was 67.5%, and 24.4% had experienced 5 or more overdoses. In the 12 months preceding 11 year follow-up 4.9% had overdosed (11.8% of those who had used heroin in that period). Of the 21 participants who had recently overdosed, 20 (95.2%) had done so overdose previously, and 19 (90.5%) were not enrolled in a treatment programme at the time. Those who had recently overdosed reported higher levels of use of opiates other than heroin (57.1 v 24.9%), benzodiazepines (61.9 v 30.5%,), methamphetamine (38.1 v 16.8%) and cocaine (19.0 v 3.7%). They also had exhibited higher levels of heroin use and other drug use at baseline, 12 and 24 month follow-ups. Conclusions: While the prevalence had declined, overdoses still occurred. A history of overdose and polydrug use patterns continued to provide strong markers for those at continued risk.
Overdose is the leading cause of premature mortality among heroin users. We examine whether the provision of regulated and quality-controlled heroin to users in specified doses would reduce heroin overdose rates. We also address this in the context of the epidemic of prescription opioid use and deaths seen in recent years in the United States and internationally. We explore the extent to which any change in legal access to heroin would affect overdose rates, and note that this depends upon the validity of the two main assumptions that variations in illicit drug purity and/or the presence of drug contaminants are major causes of overdose. Toxicological and demographic data from studies of heroin overdose deaths do not support these assumptions. The surge in the use of pharmaceutical opioids provides an example of the legal delivery of opioids of known dosage and free of contaminants, where overdose deaths can be examined to test these assumptions. Rates of fatal opioid overdose have escalated, with increased rates of prescribing of pharmaceutical opioids. On the basis of the experience with prescription opioids, unregulated legal heroin access would not reduce overdose rates.
Accountability of death to the consumption of heroin is a frequent question encountered in forensic practice. However, its difficulty is often underestimated by medical experts, since typical situations (“the syringe into the vein”) are rare or exceptional. If toxicological analyses of blood, urine and hair samples are obviously essential to establish the causal link between death and exposure to heroin, their interpretation requires special caution, whatever the performance of these analyses could be. Through a synthesis of scientific data on the pharmacology and physiology of heroin exposure, the aims of this review are to provide to practitioners guidelines for interpretation and discussion of forensic explorations, emphasizing on sampling concepts, on interpretation of opiate concentrations and on taking in consideration of contextual factors (tolerance, co-poisoning).
Ultra-rapid opioid detoxification (UROD) involves the acceleration of opioid withdrawal by administering the opioid receptor antagonist naltrexone under general anaesthesia. There is evidence from uncontrolled and a few controlled studies that UROD accelerates opioid withdrawal and that it achieves high rates of completion of acute opioid withdrawal.
However, there is clear evidence that the use of a general anaesthetic is not required to accelerate withdrawal or to achieve high rates of completion of acute opioid withdrawal. These goals can be achieved by using naltrexone or naloxone to accelerate withdrawal under light sedation, a procedure known as rapid opioid detoxification under sedation (ROD). There is also evidence that use of an opioid antagonist is not required to achieve a high rate of completion of acute opioid withdrawal. The mixed agonist-antagonist buprenorphine has achieved comparable rates of completion in similarly selected patients with fewer withdrawal symptoms. There is no evidence from controlled trials that either UROD or ROD increases the rate of abstinence from opioids 6 or 12 months after withdrawal. UROD and ROD may increase the number of patients who are inducted onto naltrexone maintenance (NM) therapy but extensive experience with NM therapy suggests that it only has a limited role in selected patients. Given the lack of evidence of substantially increased rates of abstinence, and the need for anaesthetists and high dependency beds, UROD has at best a very minor role in the treatment of a handful of opioid dependent patients who are unable to complete withdraw in any other way. ROD may have more of a role as one option for opioid withdrawal in well motivated patients who want to be rapidly inducted onto NM therapy or who want to enter other types of abstinence-oriented treatment.
This article reports on an investigation of the public health utility of media messages concerning spates (temporal clusters) of heroin-related overdose (HOD) from the perspective of some injecting drug users (IDUs). In-depth qualitative interviews were carried out with a convenience sample of 60 IDUs, in the setting of two Needle and Syringe Programs in an Australian regional city (Geelong) between April and May 2000. Very few interviewees reported that they had personally experienced a spate of overdoses. None of the interviewees reported communicating the existence of a killer batch to other IDUs. No interviewees reported having changed either their injecting practices or the amount of heroin they used following such a media alert. Indeed, a substantial minority of the interviewees reported seeking out these stronger batches and participant narratives illustrate that, for a substantial group of interviewees, the media reporting of a hypothetical ‘killer batch’ of heroin may have implications for their drug-seeking and health-related behaviour. It was found that the accuracy of information available to IDUs is mixed and that the flow of information within this social network was slow. Findings demonstrate that media reporting of killer batches of heroin has little value as a public health strategy and provide an example of how some activities that are proposed as public health measures may in fact have the opposite effect.
Objectives:
The objectives of this study were to develop and to validate a qualitative screening method that met the new Society of Hair Testing (SoHT) guideline criteria for thresholds.
Methods:
Extraction of 20 mg hair was performed by a previously validated procedure using overnight incubation in a mixture of methanol:acetonitrile:formiate buffer pH 3 (10:10:80). Analysis was performed on an Agilent 6540 quadrupole time-of-flight mass spectrometer in combination with an Agilent 1290 Infinity ultrahigh-performance liquid chromatography system. Separation was achieved with a 12-minute linear gradient chromatography on a high-strength silica T3 column at acidic conditions. An in-house database containing 30 compounds from the groups amphetamines, opiates, opioids, cocaine, benzodiazepines, and other sedatives including 6 deuterated internal standards was built by analyzing solutions from certified standards. Data were extracted using mass accuracy of ± 10 ppm, retention time deviation of ± 0.15 minutes, and area of ≥ 30,000 counts. Identification was based on scoring of retention time, accurate mass measurement, and isotopic pattern. Validation included selectivity, repeatability of analyte area, and the scoring parameters at the proposed thresholds and a method comparison with the present liquid chromatography-mass spectrometry-mass spectrometry method using 50 authentic hair samples. A daily cutoff calibrator was used to identify positive samples.
Results:
All cutoffs could be met with imprecisions of less than 5% for most parameters and analytes. Hair from drug-free subjects did not produce any positive results and the method comparison agreed in more than 90% of the cases.
Conclusions:
We conclude that the developed method meets the criteria of the new SoHT guidelines for screening cutoffs. Even though no thresholds have been suggested for benzodiazepines, we conclude that thresholds between 0.05 and 0.1 ng/mg should be sufficient to determine regular use of these substances.
Unter Opioiden versteht man neben der Untergruppe der natürlich vorkommenden Substanzen, den Opiaten, auch alle weiteren Stoffe, die in ihrem Wirkungsspektrum mit dem Morphin vergleichbar sind und halbsynthetisch oder synthetisch hergestellt werden [67]. Die medizinische Hauptwirkung eines Opioids liegt im analgeti-schen Effekt, während die missbräuchliche Anwendung als Droge auf den euphorisierenden Eigenschaften beruht. In erster Linie wird dabei Heroin (Diacetylmorphin) verwendet. Neben dem Heroin werden häufig Codein-und Dihydrocodein-Präparate missbräuchlich konsumiert. Die Schmerzlinderung und das Suchtpotenzial sind bei therapeutischer Dosierung dieser Wirkstoffe deutlich geringer als bei Heroin oder auch Morphin. Methadon wird als Heroin-Substitutionsmittel eingesetzt, andererseits aber auch illegal gehandelt und missbräuchlich konsumiert. Zusätzlich von Bedeutung sind opioidhaltige Medikamente, die insbesondere im Rahmen einer Schmerztherapie Verwendung finden. Heroin wird in der Regel halbsynthetisch durch Acetylierung der aus Rohopium gewonnenen Morphin-Base hergestellt und in Salzform als Heroin-Hydrochlorid (Heroin-HCl) dargestellt. Zusätz-liche charakteristische Alkaloide aus dem Opium sind Noscapin, Papaverin und Codein, welche ebenfalls im so genannten Straßenheroin aufzufinden sind. Analog zum Diacetylmorphin tritt dann auch Acetylcodein in den Zubereitungen auf. 4.2.1.2 Pharmakokinetik und Pharmakodynamik Heroin wird im Organismus mit einer Halbwertszeit von zwei bis neun Minuten durch Blut-und Gewebecholinesterasen und durch spontane Hydrolyse sehr rasch zu 6-Monoacetyl-morphin (6-MAM) abgebaut, das eine Plasmahalb-wertszeit von 5,3–38 Minuten aufweist. Aus 6-MAM entsteht in einer zweiten Phase Morphin (Halbwertszeit 1,1–3,1 Stunden), in einer dritten Phase wird Morphin vornehmlich zu Morphin-3-, Morphin-6-und Morphin-3,6-Glucuronid verstoffwechselt und in freier Form bzw. vornehm-lich als Glucuronid mit dem Urin ausgeschieden, des Weiteren entsteht Normorphin. Codein wird durch Glucuronidierung und Demethylierung zu Codein-6-Glucuronid, Norcodein und Morphin verstoffwechselt, das wiederum zu Normorphin bzw. zu den entsprechenden Glucuroniden umgewandelt wird. Die durchschnittliche Halbwertszeit von Codein liegt bei 2,9 Stunden (1,9–3,9 Stunden). Dihydrocodein wird in analoger Weise verstoffwechselt mit einer mittleren Halbwertszeit von 3,9 Stunden (3,3–4,5 Stunden). Eine einzelne Morphin-Injektion bewirkt bei einem psychisch gesunden Menschen außer der als wohltuend empfundenen Schmerzfreiheit keine weiteren Empfindungen. Bei Schmerzfreiheit besteht in der Regel kein Bedürfnis mehr nach einer erneuten Morphinaufnahme. Erst bei mehr-facher Morphin-Applikation tritt die euphorisierende Wirkungskomponente in den Vordergrund, so dass es insbesondere bei psychisch labi-len Personen zur Ausprägung des Morphinismus kommen kann. Die durch Morphin ausgelöste Euphorie ist gekennzeichnet durch eine ausgeglichene, ruhige, unbeschwerte und glückliche Stimmungslage, die Schwierigkeiten als unbedeu-tend erscheinen lässt und zur Gleichgültigkeit führt.
Aims: To examine drug use, crime, physical and mental health at 3 months postentry to treatment for heroin dependence.
Design: Longitudinal cohort study.
Setting: Sydney, Melbourne, and Adelaide, Australia.
Participants: Seven hundred forty-five individuals recruited on entry to treatment for heroin dependence in the 3 main treatment modalities (methadone/buprenorphine maintenance therapy; detoxification; residential rehabilitation), and 80 heroin users who were not seeking treatment at baseline.
Measurements: Structured questionnaires were used to measure drug use, crime, psychopathology, and physical health. At 3 months 10% of the cohort were randomly selected and provided a hair sample as a biologic measure of heroin use for the month preceding interview.
Findings: A 3-month follow-up rate of 88% (n=728) was achieved. There were substantial reductions in heroin use, polydrug use, injection-related risk-taking, heroin overdose, and criminal activity, as well as improvements in physical and mental health. Improvements were less marked among the nontreatment group. There was strong concordance between the cohort's self-reported heroin use and hair analysis results. Positive outcomes tended to be associated with a greater cumulative number of treatment days, and fewer treatment episodes.
Conclusions: Treatment works in the short term. Greater treatment exposure was related to improvements across a range of outcomes.
Buprenorphine is considered to have little respiratory side effects at therapeutic doses and the partial agonistic properties should produce a "ceiling effect" for respiratory depression at higher doses. Still, there are several reports on buprenorphine related deaths. Most deaths involve drug users and the co-administration of other CNS depressant drugs as well as reduced tolerance have been suggested to be risk factors. The primary aims were to investigate if lack of tolerance and/or co-ingestion of other psychotropic drugs are significant risk factors in buprenorphine fatalities. From July 2005 to September 2009, all autopsy cases where buprenorphine or norbuprenorphine had been detected in femoral blood and where analysis of buprenorphine had been performed in urine were selected. Results from the postmortem examination and toxicology were compiled. Postmortem toxicology was performed using the routine methodology at the laboratory. In total, 97 subjects were included in the study. These were divided into four groups; Intoxication with buprenorphine (N=41), Possible intoxication with buprenorphine (N=24), Control cases where buprenorphine was not the cause of death (N=14), and Unclear (N=18). The metabolite to parent compound ratios in both blood and urine in the Intoxication group were significantly different from those in the Control and Unclear groups. An extensive poly-drug use was seen in all groups with several additional opioids in the Possible group (54%) and in the Unclear group (78%) and hypnotics or sedatives in more than 75% of the Intoxication, Possible, and Unclear cases. Illicit drugs were present in all groups but not to a great extent with amphetamine and tetrahydrocannabinol as the main findings. Interestingly, 4 cases in the Intoxication group presented with no other significant drugs in blood other than buprenorphine. We conclude that a lethal concentration of buprenorphine in blood cannot be defined. Instead the analysis of blood as well as urine can be an important tool to show that the drug was taken shortly before death and to rule out a continuous use of buprenorphine supporting the notion that abstinence is an important risk factor. The presence of alprazolam in more than 40% of the Intoxications and the presence of hypnotics and sedatives in 75% of the Intoxications suggests that these drugs interact with buprenorphine producing toxic effects that buprenorphine alone would not have produced. Still, in 10% of the Intoxications no other drugs were found indicating that under certain circumstances buprenorphine alone may produce respiratory depression resulting in death.
In order to assess whether substance-abusing people show a higher risk of dying from unintentional acute intoxication in specific periods of the year, and whether this unevenly distributed risk is subject to the same seasonal influences observed in suicide cases, we studied a total of 15,792 drug-related deaths (males=14,259; females=1533) and 20,332 deaths by suicide (males=15,571; females=4761), ascertained in Italy among 15-44-year-old people from 1984 to 2000. Distribution of deaths by month was studied with circular statistic techniques, based on the maximization of mean vector length method and the Rayleigh test. The monthly distribution of deaths over the study period followed an uneven trend that clearly differed, however, between the two time-series characterizing suicides and drug-related deaths. A clear seasonal variation was found for suicides in both genders, recurring on a significant circannual cycle. No circannual cycle was observed in the monthly distribution of drug-related deaths, which seem to be influenced by non-casual oscillations following a thrice-yearly cycle, linked to a significantly more evident 6-month recurrence. Some periods of the year, however, are clearly and consistently linked to an enhanced risk of dying by unintentional, acute intoxication by illicit drugs.
Over the past decade fatal opioid overdose has emerged as a major public health issue in Australia. This report has been prepared in order to provide a comprehensive overview both of the epidemiology and circumstances of heroin overdose, and of interventions that may potentially reduce mortality from overdose.
Insect specimens collected from decomposing bodies enable forensic entomologists to estimate the minimum post-mortem interval (PMI). Drugs and toxins within a corpse may affect the development rate of insects that feed on them and it is vital to quantify these effects to accurately calculate minimum PMI. This study investigated the effects of morphine on growth rates of the native Australian blowfly, Calliphora stygia (Fabricius) (Diptera: Calliphoridae). Several morphine concentrations were incorporated into pet mince to simulate post-mortem concentrations in morphine, codeine and/or heroin-dosed corpses. There were four treatments for feeding larvae; T 1: control (no morphine); T 2: 2 microg/g morphine; T 3: 10 microg/g morphine; and T 4: 20 microg/g morphine. Ten replicates of 50 larvae were grown at 22 degrees C for each treatment and their development was compared at four comparison intervals; CI 1: 4-day-old larvae; CI 2: 7-day-old larvae; CI 3: pupae; and CI 4: adults. Length and width were measured for larvae and pupae, and costae and tibiae were measured for adults. Additionally, day of pupariation, day of adult eclosion, and survivorship were calculated for each replicate. The continued presence of morphine in meat was qualitatively verified using high-performance liquid chromatography with acidic potassium permanganate chemiluminescence detection. Growth rates of C. stygia fed on morphine-spiked mince did not differ significantly from those fed on control mince for any comparison interval or parameter measured. This suggests that C. stygia is a reliable model to use to accurately age a corpse containing morphine at any of the concentrations investigated.
A procedure is outlined for comparing dependence potential and acute toxicity across a broad range of abused psychoactive substances. Tentative results, based on an extensive literature review of 20 substances, suggested that the margin of safety ("therapeutic index") varied dramatically between substances. Intravenous heroin appeared to have the greatest risk of dependence and acute lethality; oral psilocybin appeared to have the least. Hazards due to behavioral deficits, perceptual distortion, or chronic illness were not factored into the assessments.
To examine the degree of involvement of concomitant drugs of misuse and other previously identified behavioural risk factors in acute accidental opiate-related poisoning fatalities in Sheffield, 1997-2000.
Retrospective analysis of coroners' records.
Sheffield, UK.
All those who died from an acute accidental opiate-related poisoning in Sheffield between 1 January 1997 and 31 December 2000.
Coronial data were collated under the headings: demographic characteristics, circumstances of death and toxicological findings.
Ninety-four deaths occurred over the study period. The majority of cases were regular users of illicit drugs. Approximately 20% of deaths were preceded by a period of abstinence from drug use, with imprisonment and hospitalization as the most common reasons. Sixty-one per cent of cases had concomitant drugs of misuse detected from toxicology most commonly benzodiazepines and/or alcohol. These were, however, found in relatively small concentrations and opiate blood concentrations were no lower in deaths where multiple substances were involved. Despite evidence to suggest that smoking is the preferred route of heroin administration in this region, the vast majority of cases involved injecting.
Administration of an opiate via intravenous injection was the most consistent factor associated with these deaths over the period of this study. Co-administration of other central nervous system depressants, at least in lower quantities appear to be a feature rather than a risk factor per se in such fatalities.
Making naloxone available in addicts' homes is one of several official or unofficial ways that are being tried out to reduce the rising toll of fatalities from heroin overdose.
Drug overdose is a major cause of premature death and morbidity among heroin users. This article examines recent research into heroin overdose to inform interventions that will reduce the rate of overdose death. The demographic characteristics of overdose cases are discussed, including factors associated with overdose: polydrug use, drug purity, drug tolerance, routes of administration, and suicide. Responses by heroin users at overdoses are also examined. Potential interventions to reduce the rate of overdose and overdose-related morbidity are examined in light of the emerging data in this field.
Summarizing the obtained results, the heptafluorobutyric derivatives of MOR and COD were analyzed by MS/MS-SRM, and HFBA 6-MAM by MS-SIM. Detection limits were evaluated by analyzing samples at known analyte amounts, at decreasing concentration: the concentration giving rise to an average value of S/N ratio of 3, and with a calculated concentration within 30% of the target value, was considered as the minimal concentration detectable. The obtained detection limits were: HFBA MOR, 3 pg/μl; HFBA COD, 5 pg/μl (S/N ± SD = 2.6 ± 0.8); HFBA 6-MAM, 2 pg/μl (S/N ± SD = 3.0 ± 0.4). In the case of MOR, both the SIM and the SRM techniques give the same detection limits, but they are referred to the analysis of standard solutions. If the method were applied to samples originating from complex matrices, tandem mass spectrometry would be preferable because it results in a reduction in the background noise (generally higher in biological matrices) and assures more specificity to the analysis. The experiments described above were performed in negative chemical ionization mode, but heptafluorobutyric derivatives were also analyzed by electron ionization (EI). As expected, detection limits were better than those observed in EI, because the use of negative ionization generally involves a decrement in background noise and, as a consequence, an increment in the S/N ratio. Actually, HFBA was chosen as derivatizing agent because it implies the addition of 7 or 14 fluorine atoms, which make possible the detection of analytes by negative chemical ionization. Since drugs accumulate in keratins and forensic toxicology has recently shown considerable interest in the determination of opiates in hair, hair was considered as biological matrix and analytes were extracted from matrix after acid digestion and solid-phase extraction (SPE) procedures, already reported in the literature and slightly modified in this study. Briefly, each hair sample (50 mg aliquots) was added to 0.1 N HCl, digested (45 °C, 18 h), and the solution was neutralized (0.1 M phosphate buffer, pH 6.5). After centrifugation (3500 rpm for 5 min), the supernatant was applied onto SPE columns (Bond Elute Certify, 130 mg; Varian, Harbor City, CA, USA), previously conditioned with methanol and phosphate buffer. After the washing steps (with deionized water, 0.1 N HCl and methanol) analytes were eluted by adding a freshly prepared solution of dichloromethane/isopropanol/ammonia (78:20:2, v/v/v), at a flow rate of 1 ml/min. Samples were dried under a slight flow of nitrogen, derivatized and analyzed as previously described. This analytical procedure was applied for the construction of a calibration curve, in order to verify linearity and to quantify real samples. The construction of the calibration curve requires the preparation of a series of standard samples: 50 mg aliquots from 'blank hair' were spiked with 50 μl of methanolic solutions of analytes at known concentration (0.156, 0.312, 0.625, 1.25, 2.50 and 5.00 ng/μl) and with nalorphine used as internal standard (5 ng/μl, methanolic solutions). Then samples were treated as described and analyzed by GC/NICI-MS. Each sample was analyzed in triplicate and data were elaborated using Xcalibur™ software (ThermoFinnigan). The concentration range used -(0.156-5.00 ng of analyte per mg of hair) was based on the amount of analytes expected from literature data, and on the 'cut-off' levels, i.e. the lower concentration levels below which a sample is considered negative, even if trace levels of analytes are actually found (hair cut-off level: 0.2 ng/mg). The following equation curves were obtained: MOR, y = 0.015 x + 0.0108 (correlation coefficient = R2 = 0.983); COD, y = 0.027 x + 0.0014 (R2 = 0.993); and 6-MAM, y = 0.0756 x + 0.0248 (R2 = 0.982). The values of correlation coefficients obtained for the three analytes under investigation showed good response linearity.
The leading cause of death among heroin users is drug overdose. The present study examined the relationship between history of self-reported drug overdoses and social network characteristics among cocaine and opiate users. Data were from cross-sectional surveys administered from March 2001 through February 2003 as part of follow-up of an experimental network oriented HIV prevention intervention. A total of 838 participants with histories of cocaine and opiate use completed the survey. Several social network variables were found to be significantly associated with drug overdose in the prior 2 years, including larger number of network members who were injection drug users and a larger number of conflictual ties among the network members. Even after controlling for age, gender, frequency of injection drug and alcohol use, and health status, network variables continued to have a strong association with history of recent overdose. These data suggest that large drug networks should be targeted for drug overdose prevention interventions.
This article presents a new instrument with which to assess the effects of opiate treatment. The Opiate Treatment Index (OTI) is multi-dimensional in structure, with scales measuring six independently measured outcome domains: drug use; HIV risk-taking behaviour; social functioning; criminality; health; and psychological adjustment. Psychometric properties of the Index are excellent, suggesting that the OTI is a relatively quick, efficient means of obtaining reliable and valid data on opiate users undergoing treatment over a range of relevant outcome domains.
A historical cohort study was carried out in Rome to examine overall and cause-specific mortality among intravenous drug users (IVDUs). A total of 4200 IVDUs (3411 men and 789 women) enrolled in methadone treatment centers between 1980 and 1988 were studied. There were 239 deaths during the follow-up period. The overall SMR was 10.10 in the entire cohort (95% confidence interval, 8.86-11.47), 9.30 in males and 18.07 in females. A large excess of mortality in both sexes was found for infectious, circulatory, respiratory, and digestive diseases as well as for violence, overdose, AIDS, and unknown or ill-defined causes. Tumors and suicide were excessive only in males. Deaths due to drug overdose, violence or trauma, and cirrhosis accounted for 63.6%, AIDS for 7.1%, endocarditis and other bacterial infections for 7.1%, and neoplasms for 3.8% of total mortality. These findings document serious health consequences of drug abuse in Italy.
Capillary gas chromatography with selective nitrogen detection was employed to quantify morphine and 6-monoacetylmorphine in biological fluids and tissues in five deaths attributed to heroin injection overdose. The minimum lethal concentration found was 0.021 micrograms morphine per ml of blood. In all cases, 6-monoacetylmorphine was identified in urine, confirming heroin abuse.
The aim was to quantify all cause mortality among injecting drug users.
This was a retrospective analysis of 1989 data on injecting drug users and mortality obtained from three independent agencies: the Procurator Fiscal's Office, the General Register Office, and the Scottish HIV-test register.
Greater Glasgow, Scotland.
Drug injectors, estimated population 9424.
81 names were found using the three sources to identify deaths. After removing duplicates, 51 deaths were found. This represented a mortality rate of 0.54% in the estimated population. Among female injectors the mortality rate was 0.85%, significantly higher than the rate of 0.42% among male injectors (95% CI for the true difference in mortality rates between female and male injectors was 0.31%-0.55%). Over 90% of deaths were attributed to overdose or suicide. Although AIDS caused only one death, 19% of cases (5/27) whose HIV antibody status could be ascertained were positive. The mortality rate among HIV positive injectors (3.8%) was significantly higher than among HIV negative injectors (0.49%).
Comprehensive coverage using three data sources revealed a far greater annual number of all cause deaths among injectors than would have been expected from previous research. The observed mortality rate was lower than in previous studies where the denominators used to calculate rates had an element of underenumeration. For the foreseeable future it is unlikely that AIDS will have much impact on mortality among injectors in Glasgow, because of the low prevalence of HIV infection among injectors in the city, and because HIV positive injectors are dying for reasons other than AIDS; rather, overdose and suicide will continue to be the main causes of death.
Fatal poisonings among young drug addicts (15-34 years) in the five Nordic countries, Denmark, Finland, Iceland, Norway and Sweden in 1991 were investigated and compared to a similar investigation for 1984-1985 (Sweden for 1984 only). A common definition of 'drug addict' has been applied by the participating countries. In both investigations, the greatest number of drug addict deaths was seen in Denmark calculated per 10(5) inhabitants, followed in descending order by Norway, Sweden, Finland and Iceland. An increased number of deaths was observed from 1984-1985 to 1991 in all five countries. The increase in Denmark and Sweden was small while the number of deaths was more than doubled in Norway and Finland. The increased number of cases in Norway and Sweden in 1991 is mainly due to a greater number of deaths in the age group 25-34 years. In Finland, the increased number was seen mainly in the age group 15-24 years. In the two investigations heroin/morphine caused most of the fatal poisonings in Norway and Sweden. In Denmark, heroin/morphine caused about half of the fatal poisonings only, and strong analgesics other than heroin/morphine caused about one third of the deaths. In 1984-1985 it was methadone, propoxyphene and ketobemidone and in 1991 mostly methadone. The number of heroin/morphine related deaths in Finland increased from 1984-1985 to 1991, but other drugs and poisons caused a much higher proportion of the deaths. Pentobarbital caused the only fatal poisoning in Iceland in 1991.
The purpose of the study was to analyze overall and cause-specific mortality among injection drug users in Rome.
A cohort of 4200 injection drug users was enrolled in drug treatment centers from 1980 through 1988 and followed up until December 1992.
The age-adjusted mortality rate from all causes increased from 7.8/1000 person-years in 1985/86 to 27.7/1000 in 1991/92. The rise was mainly attributable to acquired immunodeficiency syndrome (AIDS), but mortality from overdose and other causes increased as well. The cumulative risk of death by the age of 40 was 29.3%.
The impact of AIDS deaths appears to be additional to a persistent increase of mortality for all other causes.
To assess whether injecting drug users have a higher than usual risk of death from overdose in the 2 weeks after release from prison.
Soundex coding of surnames and information on date of birth were used to link entry and release dates from the local prison between 1983 and 1994 with clinical data from Edinburgh City Hospital's cohort of male injecting drug users who are infected with HIV.
Edinburgh City Hospital and Edinburgh Prison.
316/332 male injecting drug users infected with HIV in the City Hospital HIV cohort; 16 were excluded because they were enrolled after developing AIDS or because their precise date of death was not available.
Relative risk of dying from overdose before developing AIDS and relative risk of dying of all causes before developing AIDS during the 2 weeks after release from prison; this was compared with relative risks of death during other time at liberty.
238/316 (75%) injecting drug users served time in the prison between 1983 and 1994. 33 out of 316 injecting drug users who were infected with HIV died before developing AIDS during 517,177 days at risk. 20 of these men died of an overdose; 6 of these deaths occurred within 2 weeks of release during 5903 days at risk. Death rates from overdose before the development of AIDS were 1.02/1000 days during the 2 weeks after release (recently released) and 0.029/1000 days during other times of liberty. The relative risk of death from overdose became 7.7 (1.5 to 39.1) after temporal matching (when the comparison was limited to the first 2 weeks after release v the next 10 weeks). The crude relative risk in an analysis combining stratified prison term and the 2 weeks after release was 4.5 (1.7 to 11.7) for death from overdose. After temporal matching these risks became 1.8 (0.4 to 9.2).
Prisons should evaluate interventions to reduce the risk of death from overdose after release.
The coronial files of all heroin-related fatalities that occurred in New South Wales (NSW) over the period 1992-1996 were inspected. There were 953 heroin-related fatalities in NSW over the study period. There was a substantial, statistically significant increase in heroin-related fatalities over the study period, from 152 deaths in 1992 to 226 during 1996. The mean age of cases was 31.0 years, 85% were male, and 85% were classified as dependent on heroin at the time of death. There was a significant increase in the age of cases over the study period and the proportion of cases that were employed. Fatalities predominantly occurred in home settings (61%). No intervention occurred in 79% of cases. Fifty deaths (5%) occurred in the month following release from prison, 16 of which occurred the first 24 hours after release. Morphine concentrations rose from 0.24 mg/l in 1992 to 0.38 mg/l in 1996. Seventy six percent of cases involved heroin in combination with other drugs: alcohol (46%), benzodiazepines (27%), antidepressants (7%) and cocaine (7%). In only 24% of cases was morphine the sole drug detected. Males were significantly more likely to have alcohol detected at autopsy (49 vs. 24%), while females were more likely to have benzodiazepines detected (41 vs. 17%). The median blood morphine concentration among cases in which alcohol was detected was significantly lower than other cases (0.27 vs. 0.39 mg/l). It is concluded that heroin-related deaths continued to rise throughout the study period, and that deaths were predominantly among older, untreated males. Despite the rise in blood morphine concentrations, polydrug use remained the predominant toxicological pattern.
The concentrations of morphine and codeine were investigated in hair from the head, axillary and pubic regions obtained from 12 fatal heroin cases. Hair preparation involves a decontamination procedure in dichloromethane at 37 degrees C for 15 min, solubilization in sodium hydroxyde at 100 degrees C for 5 min, neutralization with hydrochloric acid and centrifugation. After extraction in chloroform-isopropanol-n-heptane (50:17:33; v/v) at pH 9.2, drugs were derivatized with BSTFA + 1% TMCS and separated on a 12-m BP-5 capillary column. Quantification was done by GC/MS using selected ion monitoring. The highest morphine concentrations were found in pubic hair (0.80 to 41.34 ng/mg), followed by hair of the head (0.62 to 27.10 ng/mg), and axillary hair (0.40 to 24.20 ng/mg). Codeine was also detected in all samples, and the codeine-to-morphine ratios ranged from 0.069 to 0.273. The differences observed in drug concentration in the 3 types of hair are discussed in the light of the existing literature. Language: en
Aim. To examine patterns and correlates of routes of heroin use among Caucasian and Indochinese heroin users. Design. A cross-sectional survey. Setting and participants. Two hundred heroin users resident in South West Sydney. The sample was divided between Caucasian and Indochinese users (each n="100)," with half of each group on methadone maintenance. Measurements. A semi-structured interview was administered, based on previous studies of transitions between routes of administration. Measures included patterns of drug use, transitions, social, health and legal issues and cultural correlates of use. Findings. Almost two-thirds (61%) had smoked heroin. Smoking was more common among the Indochinese (40% were predominantly or exclusively smokers), although injecting was the dominant route for both groups. More than one-quarter (29%) had made a transition from smoking to injecting, primarily due to drug effect and perceived cost-effectiveness. Reverse transitions were rare. Smoking appeared to be more culturally acceptable than injecting among Indochinese users. Among both groups, there was a small but significant risk for the transmission of HIV and other blood-borne viruses. Polydrug use and age were positively associated with having experienced a non-fatal overdose. Conclusions. This research documents the existence of smoking as a popular route of administration among both Indochinese and Caucasian heroin users in the study sample. There is an urgent need to provide smokers and injectors with information explaining the potential risks and ways to minimize harms associated with both routes of use.
This article presents a new instrument with which to assess the effects of opiate treatment. The Opiate Treatment Index (OTI) is multi-dimensional in structure, with scales measuring six independently measured outcome domains: drug use; HIV risk-taking behaviour; social functioning; criminality; health; and psychological adjustment. Psychometric properties of the Index are excellent, suggesting that the OTI is a relatively quick, efficient means of obtaining reliable and valid data on opiate users undergoing treatment over a range of relevant outcome domains.
In order to study differences in mortality and causes of death between HIV positive and HIV negative intravenous drug users (IVDU), 1009 (180 HIV positive and 829 HIV negative) IVDU in Oslo, Norway, were followed from their first HIV test for a mean period of 36 months (range 1–67 months). Eighty-seven (55 HIV negatives and 32 HIV positives) died during the follow-up period. The risk of death for IVDU was 31 times higher than for the general population. The estimated probability of survival after 3 years of follow-up was 0.92 for the whole cohort, 0.93 for the HIV negative group and 0.87 for the HIV positive group (P<0.001, log rank test). In a Cox regression analysis, HIV positivity, >30 years of age and >5 years of IV drug use prior to study entry were all significantly associated with a fatal outcome. Eleven per cent (n=20) of the HIV positives and 4% (n=38) of the HIV negatives died from drug overdose, which accounted for 68% of all deaths; 2.2% of the HIV positives and 0.4% (n=4) of the total cohort died from AIDS. Drug overdose represented the major threat to life among IVDU in this study. Because of the dynamics of the HIV epidemic, AIDS may have an increasing impact on mortality. However, in order to forecast the number of AIDS cases among IVDU the high non-AIDS mortality must be controlled for.
Blood samples from deceased narcotic addicts were analyzed for morphine, and the results form persons who died from narcotic addiction were compared with those from homicide victims. In most instances morphine was detectable in both types of death, and usually the values obtained were less than 30 microgram/dl. Narcotic addiction deaths involving only morphine, or morphine plus a combination of ethanol, quinine, or diazepam (Valium), were also evaluated. In some cases high quantities of ethanol were present, and death could be attributed to the combined CNS depressant effects of morphine and ethanol. The quinine levels would not normally be considered toxic, however, and it could not be ascertained that the quantity of this drug present contributed to death. Diazepam was present in elevated concentrations, and its depressant effect may have been a factor in some narcotic addiction deaths.
Radioimmunoassay of hair (RIAH) was compared with two criterion measures, confidential EMIT urinalysis and self-reporting of cocaine/heroin use, for a purposive sample of 134 persons in methadone treatment. Positive or negative RIAH was "confirmed" by urinalysis and/or self-report in 87 and 84% of the cases for cocaine and heroin (morphine), respectively. Corroborative evidence indicated that "excess" RIAH positives were attributable to the narrow window of detection for urinalysis (2 days), failure to admit drug use even to researchers, and/or inadvertent ingestion of small amounts of drug. A global self-report of cocaine use intensity was related to amount in the hair.
Toxicology analyses and other forensic science data were used to examine the mechanisms through which ethanol increased the risk for death caused by injected street preparations of heroin. The authors studied 505 victims of fatal heroin overdose and compared subjects who had concentrations of blood ethanol greater than 1000 mg/L (n = 306) with those who had concentrations less than, or equal to 1000 mg/L (n = 199). We found significant negative correlations between concentrations of ethanol and morphine (a heroin metabolite) in blood (R2 = 0.11, P = 0.0001 for log10-transformed variables) as well as between concentrations of blood ethanol and bile morphine (R2 = 0.16, P = 0.0001 for log10 bile morphine versus blood morphine). Toxicologic evidence of infrequent heroin use was more common in decedents with blood ethanol concentrations greater than 1000 mg/L than in those with lower concentrations. Our data suggest that ethanol enhances the acute toxicity of heroin, and that ethanol use indirectly influences fatal overdose through its association with infrequent (nonaddictive) heroin use and thus with reduced tolerance to the acute toxic effects of heroin.
This paper presents 245 fatal cases due to morphine and/or heroin over an 8-year period from East Denmark. All but 13 of the cases were from narcotics addicts. In 40% of the cases, only morphine was detected; in 32%, morphine and ethanol; in 19%, morphine and other drugs; and in 9%, morphine, ethanol and other drugs. Morphine concentrations in blood and liver for these four groups, and the age and sex distribution are shown. Morphine levels in blood and liver were also compared for: cases with a short survival time after the injection of morphine and/or heroin; cases from non-addicts; and cases where the drug used was obviously not the cause of death. The blood values in these groups were compared with blood concentrations found in living persons. Concentrations of morphine in stomach contents after intravenous injection of morphine and/or heroin are shown to be of the same level as in blood and liver. Ten fatal morphine cases are presented in which no morphine was detected in the urine after hydrolysis of the urine.
Data are presented on the 43 people who died over a 22-year follow-up period of a cohort of 128 heroin addicts drawn in 1969 from the newly opened London clinics. The main causes of death were drug-related, with 18 deaths specifically determined as due to overdose, of which the great majority were among people being prescribed opiates at the time. The mortality rate was a mean of 1.84% annually, and the excess mortality ratio was 11.9. This excess was highest at the beginning and varied over the period of study, appearing higher at the opening of the clinics and again in the mid-1980s. No sex differences in mortality rates were demonstrated but the excess mortality was concentrated at younger ages. No prediction of the 85 survivors could be made on the basis of length of heroin use prior to study intake, nor on age at intake.
Overdose mortality is the major adverse health effect of drug injection. The potential determinants of overdose death are poorly understood; the aim of this study was to investigate risk factors for overdose mortality among intravenous drug users (IVDU). A cohort of 4200 IVDU attending methadone treatment centres in Rome during the period 1980-1988, was enrolled. Data were collected from clinical records. Vital status and cause of death were ascertained as of 31 December 1988. A matched case-control analysis within the cohort was performed to identify risk factors of death from overdose. All overdose deaths were included as cases and four controls, matched on year of birth and sex, were selected for each case from among the cohort members still alive at the time of death of the corresponding case. In all, 81 deaths from overdose were identified as cases and compared with 324 controls. A high risk of overdose death occurred among subjects who left treatment compared with those still in treatment (odds ratio [OR] = 3.55, 95% confidence interval [CI]: 1.82-6.90). The OR was particularly elevated in the first 12 months after drop-out compared with those retained in treatment (OR = 7.98, 95% CI: 3.40-18.73). The risk of overdose death was higher for unmarried compared with married people (OR = 2.48, 95% CI: 1.31-4.68); a higher risk of overdose death was also associated with lower educational status and younger age at first drug use, but such association was not statistically significant.(ABSTRACT TRUNCATED AT 250 WORDS)
The concentrations of morphine and codeine were investigated in hair from the head, axillary and pubic regions obtained from 12 fatal heroin cases. Hair preparation involves a decontamination procedure in dichloromethane at 37 degrees C for 15 min, solubilization in sodium hydroxyde at 100 degrees C for 5 min, neutralization with hydrochloric acid and centrifugation. After extraction in chloroform-isopropanol-n-heptane (50:17:33; v/v) at pH 9.2, drugs were derivatized with BSTFA + 1% TMCS and separated on a 12-m BP-5 capillary column. Quantification was done by GC/MS using selected ion monitoring. The highest morphine concentrations were found in pubic hair (0.80 to 41.34 ng/mg), followed by hair of the head (0.62 to 27.10 ng/mg), and axillary hair (0.40 to 24.20 ng/mg). Codeine was also detected in all samples, and the codeine-to-morphine ratios ranged from 0.069 to 0.273. The differences observed in drug concentration in the 3 types of hair are discussed in the light of the existing literature.
To describe the circumstances of death and toxicological findings in all heroin-related deaths in New South Wales in 1992.
Coronial files of all cases of heroin-related deaths were reviewed. A standardised form was used to collect information on sociodemographics, history of drug use, circumstances of death, and results of toxicological analysis for each case.
152 heroin-related deaths were identified. Subjects had a mean age of 29.7 years, 82% were male, and 98% were not enrolled in a methadone treatment program at the time of their deaths. Deaths occurred in the home environment in 68% of cases and in the company of at least one other person in 58%. There was intervention before the subject's death in only 21% of cases. Two or more drug classes were detected in 71% of subjects; alcohol was detected in 45%, with a mean blood alcohol concentration of 0.14 g/100mL.
Fatal heroin overdose is potentially preventable. Educating users about the risks of co-administering alcohol and other depressant drugs with heroin, the comparative safety of injecting heroin in the company of others and the need to call for intervention sooner may reduce the frequency of heroin-related deaths.
The current paper examines critically the literature on deaths attributed to heroin overdose, and examines the characteristics and circumstances of such deaths. In particular, the dominance of the widely held belief that heroin-related fatalities are a consequence of overdose is challenged. Deaths attributed to overdose represented in the literature are typically older, heroin-dependent males not in drug treatment at the time of death. Fatalities involving only heroin appear to form a minority of overdose occasions, the presence of other drugs (primarily central nervous system depressants such as alcohol and benzodiazepines) being commonly detected at autopsy. Furthermore, deaths attributed to overdose are likely to have morphine levels no higher than those who survive, or heroin users who die from other causes. It is concluded that the term overdose is, in many cases, a misleading term, since it implies the same mechanism of death in all cases, an implication that is neither clinically useful nor consistent with published data. Implications for the prevention of heroin-related deaths are discussed.
Blood toxicology results for deaths attributed to heroin overdose during 1995 in the South Western Sydney (SWS) region (n = 39) were compared with those of a sample of 100 current SWS heroin users who had injected within the preceding 24 h. Heroin-related deaths had a higher median concentration of morphine than current heroin users (0.35 versus 0.09 mg/l). However, there was substantial overlap between the blood morphine concentrations of the two groups, ranging from 0.08-1.45 mg/l. This range incorporated 90% of heroin-related deaths. A third of current users had morphine concentrations over twice the toxic blood morphine concentration employed by the analytical laboratories, and 7% had morphine levels higher than the median recorded for fatal cases. Alcohol was detected in 51% of fatal cases (median = 0.10 g/100 ml) compared with 1% of current heroin user. There was a significant negative correlation among fatal cases between blood morphine and blood alcohol concentrations (r2 = -0.41). There was no significant difference between groups in the proportions of subjects positive for blood benzodiazepines. The results raise questions about the mechanisms of death in what are termed overdoses, and about the role of alcohol in these fatalities.
Although the total number of self poisonings in England and Wales has dropped by 32%, the number involving methadone and/or heroin rose by 900% in 1974-92. Because of concern about the role of methadone in this increase, the part played by methadone and heroin in poisoning deaths in England and Wales in 1974-92 was investigated.
A proportional mortality design was used to study whether the ratio between deaths involving methadone or heroin and other substances had increased. The time trend was examined with logistic regression.
England and Wales, 1974-92.
Accidental, undetermined, and suicidal poisoning deaths (n = 43,231).
The proportions of poisoning deaths involving methadone (alone or in combination with heroin) rose by 80% (95% CI 69%, 92%) per 3 year period. The proportion of poisoning deaths involving heroin without methadone rose by 76% (95% CI 60%, 93%) per 3 year period. Similar results were obtained when poisoning deaths were examined in relation to gender and legal category (suicide and undetermined versus accidental deaths).
The impact of opiate addiction on rates of death by poisoning is rising quickly. This may reflect the growth of the addict population and is an important public health problem. There is no evidence that methadone's involvement in these deaths has risen disproportionately in relation to that of heroin up to 1992.
Morphine analysis of hair is used in forensic toxicology to study the addiction history of heroin addicts. To clarify the features underlying fatal heroin intake, we measured hair morphine content in a group of deceased heroin addicts, to verify a possible correlation between fatal heroin overdoses and the addiction behaviour of these individuals before death.
91 deaths were attributed to heroin overdose in Verona, Italy, in 1993-96. We analysed the hair of 37 of these individuals, and of 37 active heroin addicts, 37 former heroin users abstinent from the drug for several months, and 20 individuals with no evidence of exposure to opioids. From each individual, a hair sample of about 150 mg was analysed by RIA and high-performance liquid chromatography, to measure the morphine content.
The mean morphine content in the hair of the addicts who had died was 1.15 ng/mg (SD 2.35 ng/mg; range 0-12.25 ng/mg) compared with 6.07 ng/mg (4.29; 1.15-17.0) in the active heroin addicts, 0.74 ng/mg (0.93; 0.10-3.32) in the abstinent former addicts, and values below the detection limit in the non-exposed group. Hair morphine content among those who had died was significantly lower than that in active heroin consumers (p<.00001), but not significantly different from that in the former addicts (p=0.978).
Although our findings may be subject to selection bias, since suitable hair samples were available for only 37 of the 91 addicts who had died, these findings support the theory of high susceptibility to opioid overdose after periods of intentional or unintentional abstinence, due to loss of tolerance. Medical staff running detoxification programmes should be aware of the risk inherent in relapse to heroin after a period of abstinence. Moreover, occasional heroin use without a build-up of tolerance could also give a high risk of overdose.
The use of behavioural self-reports of drug users is widespread among studies of illicit drug use. Despite widespread use, concerns about the accuracy of these reports continue to be raised. The current paper critically reviews the literature on the reliability and validity of self-reported drug use, criminality and HIV risk-taking among injecting drug users. The literature shows respectable reliability and validity of self-reported behaviours when compared to biomarkers, criminal records and collateral interviews. It concludes that the self-reports of drug users are sufficiently reliable and valid to provide descriptions of drug use, drug-related problems and the natural history of drug use.
To examine trends in rates of opioid overdose deaths from 1964 to 1997 in different birth cohorts.
Age-period-cohort analysis of national data from the Australian Bureau of Statistics.
Annual population rates of death attributed to opioid dependence or accidental opioid poisoning in people aged 15-44 years, by sex and birth cohort (in five-year intervals, 1940-1944 to 1975-1979).
The rate of opioid overdose deaths increased 55-fold between 1964 and 1997, from 1.3 to 71.5 per million population aged 15-44 years. The rate of opioid overdose deaths also increased substantially over the eight birth cohorts, with an incidence rate ratio of 20.70 (95% confidence interval, 13.60-31.46) in the 1975-1979 cohort compared with the 1940-1944 cohort. The age at which the cumulative rate of opioid overdose deaths reached 300 per million fell in successive cohorts (for men, from 28 years among those born 1955-1959 to 22 years among those born 1965-1974; for women, from 33 years among those born 1955-1959 to 27 years among those born 1965-1969).
Heroin use in Australia largely began in the early 1970s and rates of heroin use have markedly increased in birth cohorts born since 1950.
To examine patterns and correlates of routes of heroin use among Caucasian and Indochinese heroin users.
A cross-sectional survey.
Two hundred heroin users resident in South West Sydney. The sample was divided between Caucasian and Indochinese users (each n = 100), with half of each group on methadone maintenance.
A semi-structured interview was administered, based on previous studies of transitions between routes of administration. Measures included patterns of drug use, transitions, social, health and legal issues and cultural correlates of use.
Almost two-thirds (61%) had smoked heroin. Smoking was more common among the Indochinese (40% were predominantly or exclusively smokers), although injecting was the dominant route for both groups. More than one-quarter (29%) had made a transition from smoking to injecting, primarily due to drug effect and perceived cost-effectiveness. Reverse transitions were rare. Smoking appeared to be more culturally acceptable than injecting among Indochinese users. Among both groups, there was a small but significant risk for the transmission of HIV and other blood-borne viruses. Polydrug use and age were positively associated with having experienced a non-fatal overdose.
This research documents the existence of smoking as a popular route of administration among both Indochinese and Caucasian heroin users in the study sample. There is an urgent need to provide smokers and injectors with information explaining the potential risks and ways to minimize harms associated with both routes of use.
To investigate the quality of heroin seized in Vienna between 1987 and 1995 and to examine whether there was a relationship between the quality of heroin and the rate of drug-related deaths.
Reports of heroin seizure analysis and post-mortem reports of heroin-related deaths in Vienna from 1987 to 1995 were analysed.
There were 386 seizures of heroin comprising a total weight of 25 640.12 g heroin. All the seizures were in the base form. All seizures also contained a diluent, mainly lactose. Additionally, in 95 seizures caffeine, in four seizures paracetamol and in three seizures metaqualon were detected. Of a total of 764 drug-related deaths 506 cases were classified as heroin-related deaths. In 336 cases other central nervous system-depressant drugs and/or alcohol could be detected in the blood in addition to morphine (polydrug heroin-related deaths). There was evidence of a trend towards greater polydrug involvement during the study period. The age of victims of polydrug heroin-related deaths remained unchanged over time while the age of victims of pure heroin-related deaths decreased significantly. The morphine concentration in the medulla oblongata in heroin-related deaths decreased significantly. Finally, there was no statistically significant relationship between the rate of heroin-related deaths per year and the diacetylmorphine concentration of heroin seizures in that year.
The results did not substantiate the widely held belief that increases in heroin-related deaths could be explained by an increase in the quality of heroin.
To document trends in the price, purity, availability and use of heroin in New South Wales detected by the Illicit Drug Reporting System (IDRS) between 1996 and 2000, and to demonstrate the utility of the IDRS in identifying such trends.
The IDRS compares information derived from interviews with injecting drug users, key informants who work in the illicit drugs field, and key indicator data on illicit drug trends.
New South Wales, Australia.
The price of heroin approximately halved over this period, from a median of A$400 per gram in 1996 to A$220 per gram in 2000. While the price of heroin fell dramatically over the study period, the purity of police seizures of the drug was high across all years, ranging between 62% and 71%. In all years heroin was considered easy to obtain by both heroin users who purchased the drug, and by key informants from the law enforcement and health fields. Concurrent with the large fall in heroin prices, there appeared to have been an increase in the number of heroin users. Between 1997 and 1998 there was a sharp increase in the injecting use of cocaine by heroin users in NSW, a pattern that has persisted.
Regular and formal monitoring of illicit drug trends provides timely data in a systematic way to inform health and law enforcement policies towards current and emerging illicit drug problems.
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