Death from heroin overdose: findings from hair analysis

Tagliaro, Franco; Battisti, Z. De; Smith, Frederick P.; Marigo, Mario

doi:10.1016/s0140-6736(97)10101-5

Cited by 97 publications

(68 citation statements)

References 22 publications

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“…[12][13][14][36][37][38] Likewise, most participants (75.9%) did not recognize the use of heroin in situations of low tolerance as important general reasons for overdose (for example, after a period of abstinence). This cause has been recognized in numerous studies 13,14,16,[39][40][41][42] and is consistent with the fact that most overdose fatalities have relatively low blood concentrations of morphine. 12 The low perception of risk associated with the loss of tolerance and the high frequency with which this situation occurs among participants (in the last 12 months 44.1% had abstained from heroin for more than 30 consecutive days and 7.1% for 16-30 days) suggest that this factor may play an important role in the overdoses produced in the cities studied.…”

Section: Discussionsupporting

confidence: 75%

Do Young Heroin Users in Madrid, Barcelona and Seville have Sufficient Knowledge of the Risk Factors for Unintentional Opioid Overdose?

Neira-León

Barrio²,

Brugal³

et al. 2006

J Urban Health

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To identify the self-perceived reasons for unintentional opioid overdose of young heroin users in three Spanish cities and their agreement with objective risk factors for overdose. Computer-Assisted Personal Interviews (CAPI) were held with 991 streetrecruited current heroin users aged 18-30. The general reasons for overdose and the reasons for the last overdose suffered were explored with open-ended (OEQs) and precoded questions (PCQs). Limited knowledge of overdose risk factors was defined as mention of fewer than two objective risk factors for unintentional overdose in the OEQ. Univariate, bivariate, and logistic regression methods were used. 77.8% (Seville), 64.9% (Madrid) and 57.2% (Barcelona) of participants have limited knowledge of overdose risk factors. Residence in Seville and not having attended courses or meetings on overdoses were significantly associated with limited knowledge, after adjusting for other factors. The most frequently identified general reasons in OEQ or PCQ were using heroin in large amounts (66.8%), together with tranquilizers (62.0%), adulterated (60.7%), or purer than usual (57.6%). Most reasons were selected more frequently in PCQ than in OEQ, especially rapid injection of the entire dose and using heroin shortly after using tranquilizers or alcohol, by injection, or after a period of abstinence. The results were similar for overdoses suffered by participants. Most young heroin users do not have sufficient knowledge of overdose risk factors, especially the use of heroin by injection, after a period of abstinence, or together with alcohol or methadone. Specific informational or educational programs adapted to the local context are critically needed.

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Section: Discussionsupporting

confidence: 75%

Do Young Heroin Users in Madrid, Barcelona and Seville have Sufficient Knowledge of the Risk Factors for Unintentional Opioid Overdose?

Neira-León

Barrio²,

Brugal³

et al. 2006

J Urban Health

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“…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).…”

Section: Introductionmentioning

confidence: 74%

Reversal of Morphine Analgesic Tolerance by Ethanol in the Mouse

Hull

Gabra

Bailey³

et al. 2013

J Pharmacol Exp Ther

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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 coconsumption 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 who 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 [D-Ala2,N-Me-Phe4,Gly5-ol]-enkephalin (DAMGO) and morphine in the mouse tail-flick test. The reversal of morphine tolerance was partially blocked by both the gamma receptor blocker bicuculline and by the g-aminobutyric acid (GABA) B 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 GABA A antagonist bicuculline but not by the GABA B 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.

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“…For comparison, in blood specimens of heroinrelated deaths, a concentration of 0.22 mg/ml morphine has been found to be lethal (Goldberger et al, 1994), and generally a concentration of over 0.4 mg/ml methadone is sufficient to cause death in subjects tolerant to opioids (Merril et al, 1996). In most opioid addicts, the detection in hair samples of 6-monoacetylmorphine (range 0.2-5.2 ng/ mg, n ¼ 9) or methadone (range 0.4-14.2 ng/mg, n ¼ 7) indicated a long-term abuse of opiates in these subjects (at least 6-12 months before death) (see also Tagliaro et al, 1998;McLeman et al, 2000). Ethanol was found in blood samples from eight opioid addicts (0.56 7 0.28 g/l), but evidence that these subjects were not ethanol-dependent was obtained.…”

Section: Human Brain Samplesmentioning

confidence: 92%

Downregulation of Neuronal cdk5/p35 in Opioid Addicts and Opiate-Treated Rats: Relation to Neurofilament Phosphorylation

Ferrer-Alcón

Harpe

Guimón

et al. 2002

Neuropsychopharmacol

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Neuronal cyclin-dependent kinase-5 (Cdk5) and its neuron-specific activator p35 play a major role in regulating the cytoskeleton dynamics. Since opioid addiction was associated with hyperphosphorylation of neurofilament (NF) in postmortem human brains, this study was undertaken to assess the status of the cdk5/p35 complex and its relation with NF-H phosphorylation in brains of chronic opioid abusers. Decreased immunodensities of cdk5 (18%) and p35 (26-44%) were found in the prefrontal cortex of opioid addicts compared with matched controls. In the same brains, the densities of p25 (a truncated neurotoxic form of p35), phosphatase PP2Ac and m-calpain were found unaltered. Acute treatment of rats with morphine (30 mg/kg, 2 h) increased the density of cdk5 (35%), but not that of p35, in the cerebral cortex. In contrast, chronic morphine (10-100 mg/kg for 5 days) induced marked decreases in cdk5 (40%) and p35 (47%) in rat brain. In brains of opioid addicts, the density of phosphorylated NF-H was increased (43%) as well as the ratio of phosphorylated to nonphosphorylated NF-H forms (two-fold). In these brains, phosphorylated NF-H significantly correlated with p35 (r ¼ 0.58) but not with cdk5 (r ¼ 0.03). The results suggest that opiate addiction is associated with downregulation of cdk5/p35 levels in the brain. This downregulation and the aberrant hyperphosphorylation of NF-H proteins might have important consequences in the development of neural plasticity associated with opiate addiction in humans.

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Death from heroin overdose: findings from hair analysis

Cited by 97 publications

References 22 publications

Do Young Heroin Users in Madrid, Barcelona and Seville have Sufficient Knowledge of the Risk Factors for Unintentional Opioid Overdose?

Do Young Heroin Users in Madrid, Barcelona and Seville have Sufficient Knowledge of the Risk Factors for Unintentional Opioid Overdose?

Reversal of Morphine Analgesic Tolerance by Ethanol in the Mouse

Downregulation of Neuronal cdk5/p35 in Opioid Addicts and Opiate-Treated Rats: Relation to Neurofilament Phosphorylation

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