Abstract
Background: The authors present a case illustrating a mechanism leading directly to death which
is not rare but has received little attention.
Case presentation: The case was evaluated by autopsy, investigation of morphine concentration
in the blood, and clinical data. The heroin dose causing the ‚overdose‘ death of a young man who
had previously been treated a number of times for heroin addiction did not differ from his dose of
the previous day taken in the accustomed circumstances. The accustomed dose taken in a strange
environment caused fatal complications because the conditioned tolerance failed to operate. The
concentration of morphine in the blood did not exceed the level measured during earlier
treatment.
Conclusion: These results are in line with the data in the literature indicating that morphine
concentrations measured in cases of drug-related death do not differ substantially from those
measured in cases where the outcome is not fatal. A knowledge of the conditioning mechanism can
contribute to prevention of fatal cases of a similar type. The harm reduction approach places great
stress on preventive intervention based on data related to drug-related death.
Category: Englisch-Sprachige Texte
Increased drug availability can precipitate a rapid transition to compulsive drug use in both vulnerable humans and laboratory animals.
Recent studies have shown that despite equivalent levels of psychomotor sensitization, only rats with prolonged, but not limited, access
to cocaine self-administration respond to the priming effects of cocaine on drug seeking, as measured in a within-session reinstatement
model of drug craving. In this model, drug seeking is first extinguished and then reinstated by non-contingent presentations of the drug
alone in the absence of response-contingent stimuli. Here, we assessed the generality of this observation in rats with daily short (1 h, ShA)
vs long access (6 h, LgA) to i.v. heroin self-administration. As expected, heroin intake by LgA rats (n¼24) increased over time to become
excessive compared to heroin intake by ShA rats (n¼24). After escalation, LgA rats tended to be less sensitive to heroin-induced
locomotion (7.5–30 mg, i.v.) than ShA rats. In contrast, only LgA rats, not ShA rats, responded to the priming effects of heroin, as
measured by the ability of heroin alone (7.5–30 mg, i.v.) to reinstate extinguished drug-seeking behavior. Finally, during the course of
heroin intake escalation, a large proportion of LgA rats developed self-injury (mostly targeting the nails and digit tips of the forepaws), a
negative consequence not seen in ShA rats. This study reproduces and extends previous research on compulsive cocaine use by showing
that heroin-induced reinstatement is also specific to compulsive drug use and dissociable from heroin-induced reward and psychomotor
sensitization
MethadoneUsersandRiskydecisions 12
Reinforcing properties of psychoactive substances are considered to be critically involved in the development and maintenance of
substance dependence. While accumulating evidence suggests that the sensitivity to reinforcement values may generally be altered in
chronic substance users, relatively little is known about the influence reinforcing feedback exerts on ongoing decision-making in these
individuals. Decision-making was investigated using the Cambridge Risk Task, in which there is a conflict between an unlikely large reward
option and a likely small reward option. Responses on a given trial were analyzed with respect to the outcome on the previous trial,
providing a measure of the impact of prior feedback in modulating behavior. Five different groups were compared: (i) chronic
amphetamine users, (ii) chronic opiate users in methadone maintenance treatment (MMT), (iii) chronic users of illicit heroin, (iv) ex-drug
users who had been long-term amphetamine/opiate users but were abstinent from all drugs of abuse for at least 1 year and (v) matched
controls without a history of illicit substance use. Contrary to our predictions, choice preference was modified in response to feedback
only in opiate users enrolled in MMT. Following a loss, the MMT opiate group chose the likely small reward option significantly less
frequently than controls and heroin users. Our results suggest that different opiates are associated with distinctive behavioral responses
to feedback. These findings are discussed with respect to the different mechanisms of action of heroin and methadone.
Beschreibt die notwendigen Indikation fuer eine Diamorphin-Verschreibung
im Vereinigten Koenigreich (England, Wales, Scotland and the nothern of Eire!
Ebenso natuerlich die Praxis!
Heroin: What’s In the Mix?
Heroin abuse is a public health problem within the United
States. Heroin intoxication has a well-recognized toxicity
syndrome involving central nervous system depression,
respiratory depression, and pupillary constriction. However,
over the past decade, our poison control center has encountered
several heroin adulterants that changed the toxicity syndrome
observed after overdose.
In the late 1990s, contamination of heroin with the
anticholinergic drug scopolamine led to heroin overdose victims
presenting with unusual manifestations of hallucination,
mydriasis, tachycardia, and dry mucous membranes.1 More
recently, a heroin-laced acetaminophen and diphenhydramine
mixture known as “cheese” has become a popularized heroin
source for inexperienced users, and may also produce notable
anticholinergic features.2
An epidemic of naloxone-resistant heroin overdoses due to
fentanyl adulteration has led to significant morbidity and
mortality throughout the central and eastern United States.
According to records of the Philadelphia County Medical
Examiner’s office, at least 250 overdose deaths have been
associated with fentanyl between April 1, 2006, and March 1,
2007. At our poison control center, xylazine, an alpha-2
adrenergic agonist which may produce pupil constriction and
somnolence mimicking heroin effects, has also been found as an
occasional contaminant of heroin.
heroindoseandwithdrawalseverity
Hat die Route der Applikation (also Iv. oder zb. Im.) von Heroin einen Einfluss auf die schwere eines Entzuges,
wenn ja wie sieht das aus und was kann man evt. vermeiden?
Beschreibt in einer Doppel-Blind Studie den Effekt von Heroin versus Morphin.
We measured tnast-cell tryptase in postmortem blood from 22 heroin addiets
dying suddenly after injection. In 32%, the eoncentration of tryptase was
elevated (slO |J.g/l), and the mean value of tryptase was significantly
different from a control group dying from knowti, nonimtnunologic eauses
(f <0.05). The increased tryptase concentrations indicate that death was
preceded by systemic tnast-cell degranulatioti. All victims of drug deaths had
morphine in tjlood, most below 0.2 |J,g/ml. In 71% of the victims of drugrelated
deaths with tryptase values slO |j,g/l, the intermediate degradation
product, 6-monoacetyl-tnorphine, was tiot found in blood, whereas this was
the case in only two vietitns with values below that cutoff point. This indicates
that those with high tryptase concentrations survived longer than those with
lower values. No correlation was found between the IgE levels and tryptase
in either group, supporting the hypothesis that tryptase release was not
mediated by an allergie reaetion. Tlie well-known property of opiates to
stitnulate unspecifically the liberation of histamine and other constituents of
mast-cell granules offers one explatiation of our observations. Tlie results
suggest that many heroin fatalities arc eaused by an anaphylactoid reaetion.
Introduction
An estimated 25 000 heroin addicts live in the Netherlands
(population 16 000 000 inhabitants).1 Most users
(75-90%) inhale heroin (“chasing the dragon”).2 About
three quarters of these addicts are served by a comprehensive
treatment system, including various kinds of
abstinence oriented treatment facilities and a wide
range of facilities focusing on stabilisation or
minimisation of harm.1 However, 5000-8000 people
on methadone maintenance treatment regularly use
illegal heroin, have serious physical and mental health
problems, and live in socially marginalised conditions,
characterised by illegal activities and a lack of social
contacts outside the drug scene.3–5
A large cohort study in Switzerland ascertained the
feasibility, safety, and efficacy ofmedical prescription of
injectable heroin to 1969 addicts. There were considerable
improvements in physical and mental health, various
aspects of social integration, and illegal drug use in
237 patients who completed 18 months of heroin
treatment.6 Although this study indicated that heroin
assisted substitution treatment is feasible, the effectiveness
of treatment was difficult to judge because no
(random) controls were available, before and after
comparisons were restricted to those who completed
treatment, and participants were obliged to take part in
mandatory psychosocial counselling and care.7–9 In a
small randomised controlled trial (n = 51) in which
intravenous heroin was compared with some standard
treatment, functioning of the participants in the heroin
group was significantly better after six months.10 However,
these positive effects could have been the result of
the additional, and mandatory, psychosocial interventions
in the group allocated to heroin.
We examined the effectiveness of medically coprescribed
heroine in two open label randomised controlled
trials among heroin addicts who had responded
insufficiently to methadone maintenance treatment.
001_Klous_MK_et_al_2006_J_Anal_Tox
Pharmaceutical smokable heroin was developed for a clinical
trial on medical co-prescription of heroin and methadone.
This product, consisting of 75% w/w diacetylmorphine base
and 25% w/w caffeine anhydrate, was intended for use via
“chasing the dragon”, that is, inhalation after volatilization.
This procedure involves heating the powder mixture, which
may lead to formation of degradation products that could
subsequently be inhaled. We developed a method that used a
high-performance liquid chromatography system that was
compatible with photodiode-array detection and mass
spectrometric detection to separate diacetylmorphine- and
caffeine-related compounds in a wide polarity range for analysis
of the vapor. This method was used to analyze the contents of the
plastic drinking straws that were used by patients to inhale the
vapors from pharmaceutical heroin used via chasing the dragon,
which were considered to be representative of the vapors the
patients inhaled. They contained primarily unchanged
diacetylmorphine, its main metabolite 6-acetylmorphine, caffeine,
and some morphine. Several unidentified peaks were observed
in the straw chromatograms. Chemical structures were proposed
for nine degradation products: morphine derivatives with
different substitution patterns of the C3, C6, and/or N17
positions, which comprised 0.4–9.7% of the straw sample
residue weight. Activity and toxicity of most of these compounds
are unknown and require further investigation.
Summary
Contrary to what might be thought initially, the pharmacology of methadone is only partly known, and current research continues to investigate into its distinctive aspects. Clinical evidence provides key guidance to pharmacological research on the opiate system; on the other hand, evolving expectations from therapeutic drugs or putative agents for addiction treatment provide a key incentive to the broadening of pharmacological knowledge. Apart from the classic description of receptorial opioid agonism, narcotic blockade and tolerance/withdrawal dynamics, some crucial issues need to be clarified in a comprehensive way. For instance, studies have proved the importance of metabolic polymorphism in treatment planning and offered interpretations of apparent resistance to normal dosages, so authorizing the employment of high dosages on a sound pharmacological basis. Also, dosages should not be regarded as stable through time, especially in the first few months, and clinicians may schedule dose variations that take into account such expected variations while pursuing stabilization. Methadone’s action profile in the central nervous system is not exclusively based on opioid receptors, and a thorough knowledge of its ‚collateral‘ effects may explain its beneficial action against specific psychopathological abnormalities. The role of the inactive enantiomer in the context of racemous methadone’s tolerability and action profile has also been outlined. Lastly, some of the therapeutic effects of methadone endure without being neutralized by the emergence of tolerance; one of these is its crucial anticraving property. In order to clarify this issue, the mechanisms of cell membrane endocytosis and signal transduction have been illustrated and compared between different opiates
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CONTENTS
- Sexual Behaviour of Heroin Addicts in Treatment
- First Experience of Opioid Therapy with Buprenorphine in Ukraine
- Administration of Nalbuphine to Heroin Addicts. Feasibility and Short-Term Effects
- Evidence of Reliability and Validity of the Opiate Dosage Adequacy Scale (ODAS) in a Sample of Methadone Maintenance Patients
- Improvement in the Quality of Live in Heroin Addicts: Differences Between Methadone and Buprenorphine Treatment
- Methadone: A Fast and Powerful Anti-anxiety, Anti-depressant and Anti-psychotic Treatment
- Explaining Agonist Treatment Through Movie Language: The Interesting Allegory of ‘Videodrome’
- CONTENTS
Effects of Opioid Pharmacotherapy on Psychomotor and Cognitive
Performance: A Review of Human Laboratory Studies of
Methadone and Buprenorphine - The Vincent P. Dole Research and Treatment Institute for Opiate
Dependence: An Integrated Biopsychosocial Model for the
Treatment of Methadone Maintained Patients - Opioid Substitution with Methadone and Buprenorphine: Sexual
Dysfunction as a Side Effect of Therapy - Paxil (Paroxetine) in Complex Therapy in Heroin Addicts 45-54
MAYA ROKHLINA, TATIANA KITKINA AND GEORGI GUBANOV
Use of Sodium Gamma-Hydroxybutyrate (GHB) in Alcoholic
Heroin Addicts and Polydrug-Abusers
55-76
- CONTENTS
Combating the Stigma: Discarding the Label “Substitution Treatment” in Favour of “Behaviour-Normalization Treatment” - In the Service of Patients: The Legacy of Dr. Dole
- Injecting Buprenorphine Tablets: A Manageable Risk
- QTc Prolongation in Methadone Maintenance: Fact and Fiction
- Methadone: Is It Enough?
- CONTENTS
Harm reduction and specific treatments for heroin addiction.
Different approaches or levels of intervention? An illnesscentred
perspectiveMethadone Treatment in Croatia
The renaissance of methadone treatment in America
Methadone and commonplaces
Methadone maintenance and HIV infection
Breast-feeding for a methadone-maintened mother: a case
reportMethadone Maintenance treatments in European
extracommunity target
- Introduction ………………………………………………………………………………………………….8
The Clinical and Therapeutic Aspects of Personality Disorders
in Addicted Patients …………………………………………………………………………………….14
Addiction and symptoms of psychopathology ………………………………………………….14
Addiction and psychopathological dimensions ………………………………………………..14
Addiction and Personality Disorders ………………………………………………………………16
Antisocial Personality Disorder (APD) …………………………………………………………………………18
Personality and the etiopathogenesis of addiction …………………………………………..19
The self-medication hypothesis for addictive disorders …………………………………………………..19
The role of subjective effects: the self-selection hypothesis …………………………………………….20
Sensation-seeking behaviour and impairment of gratification: what is too little
or too much? ……………………………………………………………………………………………………………..21
The psychology of addiction: evolution of theoretical models. ………………………….22
Psychodynamic theories ………………………………………………………………………………………………22
Beyond psychodynamics …………………………………………………………………………………………….24
Addiction and Bipolar Spectrum ……………………………………………………………………25
Treatment of Personality Disorders during Methadone Maintenance ……………….30
Conclusions …………………………………………………………………………………………………31
The Clinical and Therapeutic Aspects of Mood Disorders
in Addicted Patients …………………………………………………………………………………….32
Epidemiology ……………………………………………………………………………………………….32
Assessment and evaluation of depression in addicted patients ………………………….34
Family History of Mood Disorders …………………………………………………………………35
Primary or secondary nature of comorbid mood disorder in relation
to addiction ………………………………………………………………………………………………….36
Impact of comorbid mood disorders on the natural course
of heroin addiction ……………………………………………………………………………………….37
Substance use among Bipolar Patients …………………………………………………………..38
Addiction and Suicide …………………………………………………………………………………..38
Heroin addiction and its consequences on mood …………………………………………….41
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