RESEARCH REPORT

Hair morphine concentrations of fatal heroin overdose cases and living heroin users
Shane Darke1, Wayne Hall1, Sharlene Kaye1, Joanne Ross1 & Johan Duou2
National Drug and Alcohol Research Centre, University of New South Wales, NSW1 and Institute of Forensic Medicine, University of Sydney, NSW, Australia2

Correspondence to: A/Prof Shane Darke National Drug and Alcohol Research Centre University of New South Wales NSW Australia E-mail: s.darke@unsw.edu.au Submitted 30 April 2001; initial review completed 19 July 2001; nal version accepted 11 January 2002

ABSTRACT Aims To compare heroin and other opiate use of heroin overdose fatalities, current street heroin users and drug-free therapeutic community clients. Design 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). Setting Sydney, Australia. Findings 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 signicant differences between males and females in hair concentrations within any of the groups. Hair morphine concentrations were correlated signicantly with blood morphine concentrations among FOD cases (r = 0.54), and self-reported heroin use among living participants (r = 0.57). Conclusions 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. KEYWORDS Hair, heroin, morphine, overdose.

INTRODUCTION The rate of fatal opioid overdoses among 1544-yearolds in Australia increased from 1.3 in 1964 to 71.5 per million in 1997, with the greatest increase occurring among older heroin users (Hall et al. 1999). Similarly large increases have been reported in other countries (Davoli et al. 1997; Neeleman & Farrell 1997; Risser et al. 2000). The typical overdose fatality, in Australia and elsewhere, is a 30-year-old-male with a long history of heroin use, who was not in treatment at the time of death
2002 Society for the Study of Addiction to Alcohol and Other Drugs

(Darke & Zador 1996; Darke et al. 2000b). In the majority of cases, central nervous system (CNS) depressant drugs other than heroin are also detected, most commonly alcohol and benzodiazepines (Monforte 1977; Kintz et al. 1989; Darke & Zador 1996; Zador et al. 1996; Darke et al. 2000b). It should be noted that heroin overwhelmingly predominates illicit opiate use in New South Wales (NSW), and in Australia generally, rather than other opiate preparations (Darke et al. 2000a). Despite the predominance of experienced, long-term heroin users among fatalities, a large proportion of fatalAddiction, 97, 977984

978

Shane Darke et al.

ities have low blood morphine concentrations (heroin is rapidly metabolized into morphine once administered) (Monforte 1977; Kintz et al. 1989; Darke & Zador 1996; Zador et al. 1996; Darke et al. 2000b). Studies have demonstrated that, in many cases, blood morphine concentrations are below, or similar to, those of living intoxicated heroin users (Darke et al. 1997), or of heroin users who died of causes other than overdose (Monforte 1977). This is puzzling, as high blood levels of morphine at autopsy would be expected in long-term users, who would presumably have a high tolerance to the CNS depressant effects of opioids. Lower morphine concentrations may, in part, relate to the use of other drugs in combination with heroin. There is a negative correlation between blood morphine and alcohol concentrations among fatal overdose cases (Steentoft et al. 1988; Ruttenber et al. 1990; Zador et al. 1996; Darke et al. 2000b), suggesting that lower doses of heroin are fatal when combined with alcohol. Other life-style factors, such as levels of recent drug use, however, may also contribute to this pattern. Until recently, it was difcult to measure recent drug use accurately, as researchers have had to rely solely upon toxicological and other data contained in coronial les. The toxicological data have consisted of blood concentrations of drugs, which provide a window on drug use only in the past 2448 hours. The development of drug detection techniques for hair samples has enabled more detailed analysis of recent drug use (Magura et al. 1992; Kintz & Mangin 1993). A recent study compared morphine concentrations detected in hair samples of fatal overdose cases, heroin users entering detoxication and incompletely abstinent former users (Tagliaro et al. 1998). Morphine concentrations in the fatal cases were signicantly lower than those of current users, but were not signicantly different from the group of incompletely abstinent former users. The authors argued that most fatalities had recommenced heroin use after a period of abstinence, and so had a lower tolerance to opioids than the active heroin-using group. The current study compared heroin and other opiate use, as assessed by morphine and 6-monoacetyl morphine (6-MAM, the specic metabolite of heroin) concentrations in hair, in the 2 months preceding either interview or death in three groups of heroin users: (1) heroin overdose fatalities (FOD); (2) current street heroin users (CU); and (3) drug free therapeutic community clients (TC). The aim was to replicate and extend the ndings of Tagliaro et al. (1998). While all overdose cases were certied by police investigation as having used heroin prior to death, and heroin is overwhelmingly the predominant opioid in NSW, opiates other than heroin may well have also been consumed in this period and contributed to hair morphine concentrations.
2002 Society for the Study of Addiction to Alcohol and Other Drugs

METHODS Cases Fatal overdose cases Permission was obtained from the NSW State Coroner to collect hair samples from suspected heroin overdose fatalities upon which autopsies were conducted at the Institute of Forensic Medicine in inner-city Sydney. All suspected heroin overdose cases presenting to the Institute of Forensic Medicine between February 1999 and October 1999 had hair samples taken at autopsy. A total of 68 cases were identied as suspected heroin overdose cases. Final autopsy reports and coronial les were then inspected for cause of death. Eligibility for inclusion as a FOD case was identical to that used in previous work by the authors: forensic pathology conclusion that death was from narcotism, circumstances of death (e.g. presence of injecting equipment) and evidence from police investigations (Darke et al. 2000b). Eight cases were rejected from the study, as forensic pathology indicated causes of death unrelated to heroin use. This left a total of 60 cases in which death was attributed to narcosis. In 18 of these cases, equipment failure at the analytical laboratory prevented analysis, leaving 42 cases in which a hair analysis was possible.

Therapeutic community clients Fifty clients from the two largest Sydney therapeutic communities were interviewed between February and August 1999, and had head hair samples taken for analysis. All living subjects were volunteers who were paid A$20 for participation in the study. It was a requirement of entry into the study that clients had been enrolled in treatment for at least 1 month prior to interview and to have at least 2 cm of head hair. All respondents were guaranteed, both at the time of screening and interview, that any information they provided would be kept strictly condential, as would the results of the individuals hair analysis. Interviews were conducted by one of the research team and took approximately 30 minutes to complete.

Current heroin users One hundred current heroin users were recruited and interviewed between May and August 1999, by means of advertisements placed in rock magazines, needle exchanges and by word of mouth. Respondents contacted the researchers, either by telephone or in person, and were screened for suitability for the study. To be eligible respondents had to have injected heroin at least six times in the preceding 6 months and at least once in the preceding month, and to have at least 2 cm of head hair.
Addiction, 97, 977984

Opiate overdose

979

Data collection forms Fatal cases The coronial les of all suspected overdose fatalities were inspected to conrm heroin overdose as the cause of death, and to record relevant case data. The standardized data collection form devised by Zador et al. (1996) was employed to record data. Information on the demographic characteristics, drug use history, circumstances of death and toxicological ndings were retrieved from the coronial les. Documents of particular relevance contained in the les were police reports, ambulance ofcers statements, witness statements, autopsy reports, transcripts of coronial inquests (where conducted) and results of toxicological analyses. Data on drug use history are not collected systematically in coronial les, although they are generally present. In NSW, all overdose cases have blood and bile samples taken at autopsy that are analysed for total morphine concentrations at the Division of Analytical Laboratories, NSW Health.

obtained reect the overall exposure to heroin in the 2 months preceding interview or death. The mean weight of analysed samples was 23.3 mg (SD 13.9, range 4127). Mean sample weights for the three groups were: TC = 28.8 mg, CU = 20.8 mg, FOD = 22.9 mg. There were no systematic differences between groups in hair colour or treatments

Analyses Hair analysis Procedures followed by the Victorian Institute of Forensic Medicine for analysis of hair morphine concentrations were identical to those employed by Tagliaro et al. (1998).

Statistical analyses Students t-tests were used for continuous data, and the c2 statistic used for the analysis of categorical data. Where distributions were skewed, log transformations were performed to allow the use of parametric statistics, including t-tests and Pearsons product moment correlations. Bile morphine concentrations were categorized into 20 mg/l range categories. Spearmans rank order correlations were conducted in correlating bile morphine concentration to other variables. All analyses were conducted using SPSS (release 9.0) (SPSS 1999).

Structured interview Therapeutic community clients and current heroin users were administered a structured interview. Areas covered by the structured interview included demographics, drug use history, overdose history and heroin use in the preceding month. Heroin use in the preceding month was measured using the opiate treatment index (OTI) (Darke et al. 1992). The OTI use a recent use episodes methodology. Estimates of heroin consumption are based upon a ratio of the number of use episodes on the two most recent use days and the two intervals between the three most recent use days. Two estimates of quantity consumed and two estimates of intervals between use are thus obtained. All interviews were conducted by two of the authors (S.K., J.R.).

RESULTS Sample characteristics The FOD group had a mean age of 32.3 years (SD 7.7, 1746), were overwhelmingly male, unemployed and not in treatment at the time of death (Table 1). Eighty-eight per cent of fatal cases were known heroin users, 81% were classied as dependent (i.e. having long-term heavy

Hair sampling A sample of 50100 hairs were taken from the posterior vertex (crown of head) of each living volunteer at the conclusion of the structured interview, with the hair being cut as close to the scalp as possible. Hair samples from the posterior vertex of overdose cases were taken at the time of autopsy. Samples were stored in plastic bags at room temperature until sent for analysis at the Victorian Institute of Forensic Medicine. Hair analyses were conducted on the 2 cm of hair closest to the scalp. Hair grows at a rate of approximately 1 cm per month (Magura et al. 1992). The current study thus analysed heroin and other opiate use over the 2 months preceding interview or death. The hair morphine concentrations
2002 Society for the Study of Addiction to Alcohol and Other Drugs

Table 1 Demographic characteristics of samples. FOD (n = 42) 32.3 (1746) 83 59 93 2 5 CU (n = 100) 28.7 (1848) 58 88 80 0 20 TC (n = 50) 28.6 (1952) 60 98 0 100 0

Variable Mean age (years) (range) % Male Unemployed (%) Treatment status (%) Not in treatment Therapeutic community Methadone maintenance

Addiction, 97, 977984

980

Shane Darke et al.

involvement in the heroin life-style) and 19% as recreational users. In all cases, the route of heroin administration was by injection. One case was a death in custody, one case was in periodic detention at the time of death, and two cases were suicides. The median blood morphine concentration of cases was 0.35 mg/l (range 0.1012.0 mg/l), and 66% had bile morphine concentrations greater than 20 mg/l (range 0- >100 mg/l). In 82% of cases drugs other than morphine were also detected. The most common drugs detected in addition to morphine were alcohol (50%, median BAC = 0.12 g/100 ml), benzodiazepines (28%) and cocaine (18%). Fifty-six per cent of cases were known to be heavy alcohol users. There was a signicant negative correlation between log blood morphine and log blood alcohol concentrations (r = 0.29, P < 0.05). In terms of key demographic and toxicological variables, the FOD group were similar to people in NSW who died of heroin overdose between 1992 and 1996 (Darke et al. 2000). There were no signicant differences between FOD cases and overdose cases in which equipment failure prevented analysis being conducted in: age (32.3 versus 33.4 years), percentage male (83 versus 82%) or percentage classied as a dependent heroin user (81 versus 92%). The average age in both the CU and TC groups was in the late twenties, and both groups consisted predominantly of unemployed males. Eighty per cent of the CU group were not in treatment at the time of interview. The remaining 20% were enrolled in methadone maintenance, but were active heroin users and met criteria for inclusion in the study. Among the CU group, 79% were daily heroin users, 16% used more than weekly but less than daily, and 5% used less than weekly. Among TC subjects, 88% reported no heroin use in the preceding month, with the remainder reporting sporadic use over that period. Both the CU and TC groups had high levels of polydrug use. The CU group had used a mean of 9.0 drug classes in their life-time (SD 1.7, range 411) and 6.1 (SD 2.0, range 210) in the preceding 6 months. Similarly, the TC group had used a mean of 9.7 drug classes in their life-time (SD 1.2, range 711) and 5.4 (SD 2.1, range 19) in the preceding 6 months. Opiates other than heroin had been used sporadically in the preceding 6 months: CU (41% used, median used days = 6), TC (44% used, median used days = 17). Sixty per cent of the CU and TC groups reported no alcohol use in the preceding 6 months, with l% reporting daily use and 16% more than weekly use. A history of at least one non-fatal overdose was reported by 68% of the TC group and 54% of the CU group. The demographic and drug use characteristics of these groups were consistent with other recent
2002 Society for the Study of Addiction to Alcohol and Other Drugs

Australian studies of heroin users (Swift et al. 1999; Darke et al. 2002). The FOD group was signicantly older than both the CU (32.3 versus 28.7, t140 = 2.8, P < 0.01) and TC (32.3 versus 28.6, t88 = 2.3, P < 0.05) groups. The CU and TC groups did not differ signicantly in age. There were signicantly more males in the FOD group than in either the CU (83 versus 58%, 2, 1 df = 8.4, P < 0.01) or TC (83 versus 60%, 2, 1 df = 6.0, P < 0.05) groups. There was no signicant gender difference between the CU and TC groups. The FOD group were less likely than either the CU (59 versus 88%, 2, 1df = 15.5, P < 0.001) or TC (59 versus 98%, 2, 1df = 22.1, P < 0.001) groups to be unemployed. The latter two groups did not differ signicantly in employment status.

Hair morphine concentrations Median group hair morphine and 6-MAM concentrations are presented in Table 2. Morphine was detected in the hair of 98% of the CU group, 100% of the FOD group and 72% of the TC group. 6-MAM was detected in 71% of the CU group, 26% of the FOD group and 26% of the TC group. There were large differences between the three groups, with the CU group having a median hair morphine concentration approximately four times that of the FOD group, who in turn had a concentration approximately six times that of the TC group. Due to the skewness of the hair morphine concentration distributions, log transformations were conducted, and t-tests performed between the group mean log hair concentrations. The CU group had a signicantly higher mean log hair concentration than both the FOD (t140 = 4.1, P < 0.001) and TC (t148 = 7.9, P < 0.001) groups, while the FOD group had a signicantly higher mean log hair concentration than the TC group (t90 = 3.3, P < 0.001). When analyses are restricted solely to cases in which 6-MAM was detected, a similar patten emerged. The CU group had a signicantly higher mean log 6-MAM hair concentration than both the FOD (t80 = 2.27, P < 0.05) and TC (t82 = 2.87, P < 0.05) groups, while the FOD and TC groups did not differ signicantly. The small numbers involved in the last analyses should be borne in mind. The distributions of hair morphine concentrations among the three groups are presented in Fig. 1. The large difference between the CU and other groups is illustrated by the 22% of the CU group who had hair morphine concentrations over 5 ng/mg, compared to only 2% of both the FOD and TC groups. There were no signicant differences between males and females in mean log hair concentrations in the TC, CU or FOD groups. Age and log hair morphine concentrations were not signicantly correlated in any of the
Addiction, 97, 977984

Opiate overdose
Table 2 Median hair morphine concentrations (range in brackets). Group CU Morphine (n = 100) 6-MAM (n = 71)a FOD Morphine (n = 42) 6-MAM (n = 11)a TC Morphine (n = 50) 6-MAM (n = 13)a

981

Median hair morphine concentration (ng/mg) Males Females Persons

2.10 (0.0023.00) 0.47 (0.102.30) 0.53 (0.0931.00) 0.16 (0.051.20) 0.14 (0.004.00) 0.15 (0.120.45)

2.10 (0.0021.00) 0.42 (0.103.30) 1.00 (0.224.10) 0.51 (0.070.63) 0.08 (0.005.10) 0.23 (0.085.10)

2.10 (0.0023.00) 0.42 (0.103.30) 0.53 (0.0931.00) 0.33 (0.051.20) 0.09 (0.005.10) 0.15 (0.085.10)

Cases in which 6-MAM was detected.

Figure 1 Distribution of hair morphine concentration among fatal overdose cases, current heroin users and therapeutic community clients

three groups: TC (r = 0.08), CU (r = 0.03) and FOD (r = 0.02). There was a signicant positive correlation among the FOD group between log hair and log blood morphine concentrations (r = 0.54, P < 0.001). There was no signicant correlation between hair morphine concentration and bile morphine concentration (rs = 0.08) or between blood morphine and bile morphine concentrations (rs = 0.23). There was a signicant positive correlation among living users (i.e. CU and TC) between self-reported heroin use and log hair morphine concentrations (r = 0.57,
2002 Society for the Study of Addiction to Alcohol and Other Drugs

P < 0.001), and between self-reported heroin use and log 6-MAM hair morphine concentrations (r = 0.54, P < 0.001).

DISCUSSION The major nding of the current study was the large difference between the three groups in recent heroin and other opiate consumption levels, as indicated by hair morphine concentrations. Current heroin users had a
Addiction, 97, 977984

982

Shane Darke et al.

median hair morphine concentration four times that of the fatal overdose cases, indicating substantially heavier recent opiate use. The fatal cases, however, were not abstinent in the period prior to death, as the median morphine concentration of this group was in turn six times that of the therapeutic community clients, but they had used considerably less heroin and other opiates than active street users. As noted previously, the hair morphine concentrations cannot be used to indicate which specic opiates had been used by participants in the preceding 2 months. This, however, is not important. It is exposure to opiates per se that is of relevance here. However, it should be noted that even when the analyses are restricted to 6-MAM, the specic metabolite of heroin, the current user group had signicantly higher concentrations of 6-MAM than the fatal overdose cases. It is important to note that the demographic characteristics and toxicological ndings of the fatal overdose cases were similar to those of NSW overdose cases reported in other studies (Darke et al. 2000b). In terms of key variables such as age, sex, employment, treatment status, prison status and blood toxicology, this was a typical group of NSW overdose cases. Similarly, the demographics and drug use of the living heroin users were consistent with other studies of NSW heroin users (Swift et al. 1999; Darke et al. 2002). Consistent with the epidemiological data on opiate use in NSW, the use of opiates other than heroin among current users was sporadic, having been used by less than half of the group, and with median frequency monthly use. In contrast, 79% were daily heroin users. The results of the study are similar to those reported by Tagliaro et al. (1998), but with some important differences. In the Tagliaro study, there was no signicant difference between the hair morphine concentrations of the fatal overdose cases and incompletely abstinent controls, leading the authors to conclude that most fatalities had recommenced heroin use after a period of virtual abstinence, and so had a lower tolerance to opioids than the active heroin using group. The current results do not support the conclusion that these cases were abstinent from heroin and other opiates. Rather, they suggest that the fatal cases were still using heroin and other opiates, but at a lower degree of chronic intake. It should also be noted that the incompletely abstinent controls in the Tagliaro et al. (1998) study had a mean hair morphine concentration of 0.74 ng/mg, compared to the median value of 0.09 ng/mg reported among the TC group in the current study. The control group of incompletely abstinent controls in the Tagliaro et al. (1998) study thus appeared to be using more heroin and other opiates than the control group of TC clients from the current study. In comparing the two studies, however, there are methodological differences which should be borne in
2002 Society for the Study of Addiction to Alcohol and Other Drugs

mind. The analytical methods employed for hair analysis were identical in the two studies. However, hair samples in the Tagliaro et al. study varied from 3 to 5 cm in length, meaning that morphine concentrations related to heroin and other opiate use over different times for different individuals. No group data were presented, so it is unclear whether there were systematic differences in measured hair length between groups. The current study restricted measurements to 2 cm of hair for all subjects, so heroin and other opiate use for all groups and individuals was measured over an equivalent period. It is thus not possible to directly compare morphine concentrations from the two studies. The fact that the FOD group of long-term users did not appear to be using as much heroin and other opiates as the current users may reect the natural history of heroin use. The rigours of the heroin life-style may mean that after a decade or more of heroin use, many users cut down their use, although remaining regular, dependent users of heroin and other opiates. The low blood morphine concentrations detected in many fatal overdose cases may thus reect less frequent use, and correspondingly lower and less stable tolerance to opioids. The potential role of alcohol in these fatal heroin overdose cases should not be ignored. While not strictly comparable, the comparative gures on alcohol consumption suggest a much higher prevalence of alcohol use among fatal cases than the broader heroin using population. A recent comparative study of the blood toxicology of fatal overdose cases and current street heroin users provides support for this assertion (Darke et al. 1997). It is possible that many of the overdose cases in these two studies were compensating for their reduced heroin and other opiate use by increasing their alcohol use. The lower heroin and other opiate use of the fatal cases in the current study, and the associated lower tolerance, would increase the risk of an overdose in the presence of alcohol. It is important to note the negative correlation between blood alcohol and morphine concentrations among fatal cases, which is consistent with earlier research (Steentoft et al. 1988; Ruttenber et al. 1990; Zador et al. 1996; Darke et al. 2000b). It is worthy of note that there were no sex differences in hair morphine concentration in any of the three groups. The use patterns of males and females appeared comparable. If this is so, why are males so heavily overrepresented among fatal overdose cases? It would appear that male and female overdose cases were using at the same lower levels compared to current users, and so would be at a similar level of risk due to reduced tolerance. However, it has been demonstrated repeatedly that substantially higher proportions of male overdose fatalities have alcohol detected (Darke & Zador 1996; Darke et al. 1997; Darke et al. 2000b). In the current study, 58%
Addiction, 97, 977984

Opiate overdose

983

of male overdose cases had alcohol detected, compared to 14% of the females. A combination of low tolerance and alcohol use may expose older male heroin users to substantially greater risk of overdose than females. The role of alcohol among male heroin users, and its relationship to overdose, is clearly one of signicance to clinicians. Further research on the nature of the relationship between alcohol, heroin overdose and gender is clearly warranted. The study by Tagliaro et al. (1998) did not nd a signicant correlation between blood and hair morphine concentrations, which may reect the fact that the time frame over which heroin and other opiate use was measured varied from individual to individual. The current study found a 0.54 correlation between these two variables. Heroin and other opiate consumption prior to death in the current study was thus associated with blood morphine concentration detected upon death. Finally, the results of the current study are also relevant to the validity of self-reported drug use among heroin users in research studies. There was a strong correlation between hair morphine concentrations and selfreported heroin use in the preceding month (the period covered by the OTI), and between 6-MAM hair concentrations and self-reported heroin use. The literature on the validity of self-reported drug use among IDU has shown self-reported drug use to have high degrees of concurrent reliability and validity (Darke 1998). The current study is consistent with these studies. The correlation between hair and bile morphine concentrations, however, was not signicant. Bile morphine concentration is routinely reported in toxicological reports of NSW overdose fatalities. Higher bile morphine concentrations are assumed to indicate longterm, chronic opiate use (Hepler & Isenschmid 1998). The current study indicates that bile morphine concentrations should be treated cautiously, a point made by other authors (Agarwal & Lemos 1996). The absence of a signicant statistical relationship between heroin and other opiate consumption in the preceding two months and bile readings suggests that bile may be a poor marker for morphine consumption, and a poor diagnostic indicator of dependent opiate use. For coronial matters involving the determination of recent opiate consumption, hair analysis would appear to provide a more accurate measure than reliance upon bile concentration. The prole of overdose cases as typically older, untreated heroin users who are using less opiates than current street users poses the question of how to reduce overdose mortality among this group. As the current data illustrates, it is unusual for fatal heroin overdose cases to be enrolled in a treatment programme. In fact, one previous study of overdose fatalities reported that three-quarters of cases had never been enrolled in
2002 Society for the Study of Addiction to Alcohol and Other Drugs

methadone maintenance, the primary treatment modality in Australia (Zador et al. 1996). The recruitment to treatment of at risk older heroin users may substantially reduce overdose mortality and morbidity. While public attention tends to focus on younger heroin users it is older heroin users, who are using less heroin and other opiates, that are at greatest risk. Targeted education about the role of alcohol in overdose may also help reduce morbidity, particularly among male heroin users. In summary, the current study found that fatal overdose cases were not abstinent from opiates in the period prior to death, but were using considerably less heroin and other opiates than active street users. Fatal overdose cases appeared to have been at risk from a lower tolerance to opiates and a higher level of alcohol consumption. This group represents a high priority for recruitment into treatment if overdose mortality is to be substantially reduced.

ACKNOWLEDGEMENTS This research was funded by the Commonwealth Department of Health and Aged Care and the NSW Department of Health. The authors wish to thank the staff at WHOS, Odyssey House, the Kirketon Road Centres, the Glebe Coroners Court, the NSW Institute of Forensic Medicine and the Victorian Institute of Forensic Medicine and the Drug Intervention Service Cabramatta.

REFERENCES
Agarwal, A. & Lemos, N. (1996) Signicance of bile analysis in drug-induced deaths. Journal of Analytical Toxicology, 20, 6163. Darke, S. (1998) Self-report among injecting drug users: a review. Drug and Alcohol Dependence, 51, 253263. Darke, S., Hall, W., Heather, N., Wodak, A. & Ward, J. (1992) Development and validation of a multi-dimensional instrument for assessing outcome of treatment among opioid users: the Opiate Treatment Index. British Journal of Addiction, 87, 593602. Darke, S., Ross, J., Hando, J., Hall, W. & Degenhardt, L. (2000a) Illicit Drug Use in Australia: Epidemiology, Use Patterns and Associated Harm. National Drug Strategy Monograph no. 43. Canberra: Commonwealth Department of Health and Aged Care. Darke, S., Ross, J., Zador, D. & Sunjic, S. (2000b) Heroin-related deaths in New South Wales, 199296. Drug and Alcohol Dependence, 60, 141150. Darke, S., Sunjic, S., Zador, D. & Prolov, T. (1997) A comparison of blood toxicology of heroin-related deaths and current heroin users in Sydney, Australia. Drug and Alcohol Dependence, 47, 4553. Darke, S., Topp, L., Kaye, S. & Hall, W. (2002) Heroin use in New South Wales, Australia, 19962000: 5-year monitoring of
Addiction, 97, 977984

984

Shane Darke et al.

trends in price, purity, availability and use from the Illicit Drug Reporting System (IDRS). Addiction, 97, 179186. Darke, S. & Zador, D. (1996) Fatal heroin overdose: a review. Addiction, 91, 17571763. Davoli, M., Perucci, C. A., Rapiti, E., Bargagli, A. M., Dippoliti, D., Forastiere, F. & Abeni, D. (1997) A persistent rise in mortality among injection drug users in Rome, 1980 through 1992. American Journal of Public Health, 87, 851853. Hall, W., Degenhardt, L. & Lynskey, M. (1999) Opioid overdose mortality in Australia, 196497: birth-cohort trends. Medical Journal of Australia, 171, 3437. Hepler, B. R. & Isenschmid, D. S. (1998) Specimen selection, collection, preservation and security. In: Karch, S. B., ed. Drug Abuse Handbook, pp. 873889. Boca Raton, FL: CRC Press. Kintz, P. & Mangin, P. (1993) Opiate concentrations in human head, axillary and pubic hair. Journal of Forensic Sciences, 38, 657662. Kintz, P., Mangin, P., Lugnier, A. A. & Chaumont, A. J. (1989) Toxicological data after heroin overdose. Human Toxicology, 8, 487489. Magura, S., Freeman, R. C., Siddiqi, Q. & Lipton, D. S. (1992) The validity of hair analysis for detecting cocaine and heroin use among addicts. International Journal of the Addictions, 27, 5169. Monforte, J. R. (1977) Some observations concerning blood morphine concentrations in narcotic addicts. Journal of Forensic Sciences, 22, 718724.

Neeleman, J. & Farrell, M. (1997) Fatal methadone and heroin overdoses: time trends in England and Wales. Journal of Epidemiology and Community Health, 51, 435437. Risser, D., Uhl, A., Stichenwirth, M., Honigschnabl, S., Hirz, W., Schneider, B., Stellwag-Carion, C., Klupp, N., Vycudilik & Bauer, G. (2000) Quality of heroin and heroin-related deaths from 1987 to 1995 in Vienna, Austria. Addiction, 95, 375382. Ruttenber, A. J., Kalter, H. O. & Santinga, P. (1990) The role of ethanol abuse in the etiology of heroin-related death. Journal of Forensic Sciences, 35, 891900. SPSS Inc. (1999) SPSS Release 9.0. Chicago: SPSS Inc. Steentoft, A., Worm, K. & Christenson, H. (1988) Morphine concentrations in autopsy material from fatal cases after intake of morphine and/or heroin. Journal of the Forensic Science Society, 28, 8794. Swift, W., Maher, L., Sunjic, S. & Doan, V. (1999) Transitions between routes of heroin administration: a study of Caucasian and Indochinese heroin users in Southwestern Sydney, Australia. Addiction, 94, 7182. Tagliaro, F., Debattisti, Z., Smith, F. P. & Marigo, M. (1998) Death from heroin overdose: ndings from hair analysis. Lancet, 351, 19231925. Zador, D., Sunjic, S. & Darke, S. (1996) Heroin-related deaths in New South Wales, 1992: toxicological ndings and circumstances. Medical Journal of Australia, 164, 204 207.

2002 Society for the Study of Addiction to Alcohol and Other Drugs

Addiction, 97, 977984