Heroin is More Than Just Diamorphine

Heroin isn't just heroin anymore. Over the last two decades, there has been diversification in the forms and ‘brands’ of heroin which exist in both the domestic as well as international marketplaces. Closer examination reveals important differences between these ‘brands’. Black market heroin may now be obtained in either the form of salt (hydrochloride) or the separated base. Importantly, the different forms have different suitabilities for use by injection or by ‘chasing the dragon’, with the salt form being most suitable for injecting, whilst many of the base forms are either used by ‘chasing’ or are chemically transformed to the salt before injection. Country of origin and obvious physical characteristics such as colour are strong predictors of ‘salt’ or ‘base’ status. When consideration is given to the more recent technique of chasing the dragon, a new interpretation can be attached to some of the other drugs found in samples of black market heroin (often described as ‘impurities’). New data have identified that several of these additional drugs increase substantially the proportion of heroin which sublimates and can successfully be recovered by the heroin ‘chaser’, and these increases can be seen in the extent of recovery of both salt and base forms of heroin. Finally, new policy options are explored in the light of this new evidence-options that include the proposed development and promotion of NIROAs (non-injectable routes of administration), and the possible constructive manipulation of the heroin marketplace through differential application of interdiction efforts so as to promote the move from injecting to ‘chasing’ as the chosen method of heroin use.     

DIFFERENT FORMS OF HEROIN AND THEIR RELATIONSHIP TO COOK-UP TECHNIQUES: DATA ON,AND EXPLANATION OF,USE OF LEMON JUICE AND OTHER ACIDS

Recent reports of the use of lemon juice in the preparation of heroin for injection have failed to recognize the importance of the different forms of heroin (in the form of the salt or the base) and the impact of this on the chemical manipulation required before injection. One hundred and four opiate addicts in London were interviewed about the forms of heroin (white, brown, etc) and their relationship to cook-up techniques (use of heat and acid). White heroin was typically prepared with water and heat; brown heroin was prepared with acid (citric acid or Vitamin C (ascorbic acid) or lemon juice) and heat; pharmaceutical heroin was prepared with water only (i.e. neither acid nor heat). On the last occasion of heroin use, brown heroin had been the form most commonly used, with over 90% of the sample using citric acid or vitamin C. Lemon juice was rarely used, and heat was almost universally applied in conjunction with lemon juice.     

Different forms of heroin and their relationship to cook-up techniques: data on, and explanation of, use of lemon juice and other acids.

Recent reports of the use of lemon juice in the preparation of heroin for injection have failed to recognize the importance of the different forms of heroin (in the form of the salt or the base) and the impact of this on the chemical manipulation required before injection. One hundred and four opiate addicts in London were interviewed about the forms of heroin (white, brown, etc) and their relationship to cook-up techniques (use of heat and acid). White heroin was typically prepared with water and heat; brown heroin was prepared with acid (citric acid or Vitamin C (ascorbic acid) or lemon juice) and heat; pharmaceutical heroin was prepared with water only (i.e. neither acid nor heat). On the last occasion of heroin use, brown heroin had been the form most commonly used, with over 90% of the sample using citric acid or vitamin C. Lemon juice was rarely used, and heat was almost universally applied in conjunction with lemon juice.     

Heroin self-administration by means of 'chasing the dragon': pharmacodynamics and bioavailability of inhaled heroin.

In this controlled clinical study, the bioavailability and pharmacodynamics of inhaled heroin are evaluated and compared between 'chasing the dragon' and inhalation from a heating device, and at three dose levels, 25, 50 and 100 mg heroin, in two separate study phases. In study phase 1, no differences between the inhalation methods were detected on any of the physiological or behavioral measures, nor in bioavailability. Subjectively, the participants had a strong preference for the method of chasing, which was therefore used in study phase 2. In phase 2, heroin produced a dose-related increase in subjective drug-liking, body temperature and heart rate, and a clear, dose-related decline in reaction time. Linearly dose-related differences were found in the amount of total morphine in urine, amounting to an average of 45% of the parent heroin base received. Based on these findings, it is concluded that chasing is quite an effective route of heroin administration, producing rapid, dose-related subjective and objective effects and a sufficiently high and reproducible bioavailability.     

Heroin. II. Preparation, hydrolysis, stability, pharmacokinetics

Heroin is prepared by treating morphine with acetyl chloride or acetic anhydride. It is a simple reaction and the yields are generally quantitative. Nowadays the whole process is illegal. Morphine is the major alkaloid present in the opium poppy. Opium is manufactured illicitly then morphine is extracted from it in clandestine laboratories. Numerous studies were carried out on heroin to investigate its rate of hydrolysis. It has been shown that heroin is rapidly deacylated in aqueous solution at alkaline or acidic pH to form 6-acethylmorphine and finally, to morphine. Heroin also rapidly decomposes in biological medium yielding first 6-acetylmorphine and then morphine. Hydrolysis can be performed in blood and in tissue homogenates. Heroin can be administered by several routes. Smoking and intravenous administration are preferred, but intranasal, intramuscular and subcutaneous administration are also common. Recently, there has been a shift in heroin use patterns from injection to sniffing and smoking. Sharing of the injection equipment can result in several severe infectious diseases, such as AIDS, hepatitis B and C. Soon after administration, heroin metabolizes to 6-acetylmorphine and morphine. Most of the pharmacological activities of heroin are due to these active metabolites. Therefore, knowledge of distribution of 6-acetylmorphine and morphine is essential to understand pharmacological properties of heroin. Heroin, which is relatively nonpolar compound compared with morphine, has high lipid solubility facilitating rapid absorption from the bloodstream and passage through the blood-brain barrier. When heroin is administered by intravenously the drug takes 10 s to reach the brain i.e. pharmacological effects appear quickly.     

Changes in patterns of drug use among injecting drug users following changes in the availability of heroin in New South Wales, Australia

The aim of this study was to examine changes in drug use patterns among groups of injecting drug users (IDU) who remained in the drug market during a period of reduced heroin availability in NSW, Australia. Cross-sectional data collected from regular IDU interviewed as part of the NSW Illicit Drug Reporting System (IDRS) between 1996 - 2003 were analysed. Drug use patterns, reported drug availability and price were assessed. There was a marked decrease in the frequency of heroin use during the period of reduced availability in 2001, with some increase in 2002 and 2003. Heroin availability and frequency of use have not returned to levels reported prior to 2001; however; even at the peak of the reduction in supply, users continued to access heroin. There was a significant shift among IDU from heroin to cocaine during 2001, which subsequently reversed. The availability of cocaine has fluctuated in recent years, but the price has remained stable. The price of heroin appeared to be more responsive to market fluctuations, and co-varied with heroin availability. IDU used cocaine when heroin was less available; however, patterns of cocaine use were not maintained. The frequency of heroin use remained lower, which may be indicative of a less consistent supply, increased price or increased numbers of IDU entering treatment. The reduced supply of heroin in 2001 highlighted the adaptable nature of IDU patterns of use, indicative of the need for a commensurate treatment response. It also highlighted the importance of the ongoing monitoring of drug trends in Australia. [Roxburgh A, Degenhardt L, Breen C. Changes in patterns of drug use among injecting drug users following changes in the availability of heroin in New South Wales, Australia. Drug Alcohol Rev 2004;23:287-294]     

Heroin Use,Dependence, and Attitudes to Treatment in Non-Treatment-Seeking Heroin Users: A Pilot Study

Much research examining heroin users utilizes treatment samples; non-treatment-seeking heroin users are not well understood. It is unclear whether this group can avoid impaired control or negative sequelae commonly observed in treatment-seeking populations. During 2000 and 2001, we recruited 69 non-treatment-seeking heroin users with no treatment history. Heroin use, management strategies, treatment attitudes, and risk behaviors were assessed; the DSM-IV checklist and severity of dependence scale were completed. Study limitations and implications for heroin use and its treatment are discussed. This study was funded by Prince Charles Hospital Foundation.     

Multiple risks for HIV and hepatitis B infection among heroin users

This study investigates the extent to which heroin users are exposed to multiple forms of infection risk. Structured interviews were administered to a prospective network sample of 408 heroin users. Subjects were contracted in south London in a wide range of social settings by specially recruited privileged access interviewers. Most heroin users (74.5%) had been exposed to more than one infection risk factor and more than half of the sample had been exposed to three or more risk factors. HIV serostatus was primarily related to men having sex with men. Hepatitis B seropositive status was primarily related to the number of years injecting drugs. At this stage of the HIV epidemic in London, HIV infection among heroin users may be related more to homosexual risk behaviour than drug risk factors. Heroin injectors were at greater risk of infection than heroin chasers both through their sexual behaviour as well as through their injecting practices. Heroin users who refused to give a saliva sample for analysis were found to be more likely to engage in several health risk behaviours than those who provided samples. This finding has important methodological implications for seroprevalence surveys. Other implications of the results for prevention programmes aimed at health risk behaviours of heroin users are also discussed.     

Heroin addiction

Heroin is an illicit, highly addictive drug. It is either the most abused or the most rapidly acting member of opioids. Abusers describe a feeling of a surge of pleasurable sensation, named as "rush" or "high". Repeated administration of high doses of heroin results in the induction of physical dependence. Physical dependence refers to an altered physiological state produced by chronic administration of heroin which necessitates the continued administration of the drug to prevent the appearance of a characteristic syndrome, the opioid withdrawal or abstinence syndrome. Withdrawal symptoms may occur within a few hours after the last administration of heroin. Symptoms of the withdrawal include restlessness, insomnia, drug craving, diarrhea, muscle and bone pain, cold flashes with goose bumps, and leg movements. Major withdrawal symptoms peak between 48 and 72 hours after the last dose of heroin and subside after about a week. At this time, weakness and depression are pronounced and nausea and vomiting are common. Nevertheless, some chronic addicts have shown persistent withdrawal signs for many months or even years. Heroin addiction is considered as a behavioural state of compulsive drug use and a high tendency to relapse after periods of abstinence. It is generally accepted that compulsive use and relapse are typically associated with the status of heroin craving or heroin hunger that are difficult to define but appear to be powerful motivational significance in the addiction process. The route of administering heroin varies largely and may indicate the degree of seriousness of the individual's addiction. Intravenous administration seems to be the predominant method of heroin use, but recently a shift in heroin use pattern has been found, i.e. from injection to sniffing and smoking. Frequent injections coupled with widespread sharing of syringes increase the risk of contracting HIV, hepatitis B, C and other blood-borne infectious diseases. Long-term use of heroin has also severe medical consequences such as scarred veins, bacterial infections of blood vessels, liver and kidney diseases, and lung complications.     

Effect of repeated administrations of heroin, naltrexone, methadone, and alcohol on morphine glucuronidation in the rat

Rationale Heroin is rapidly metabolized to morphine that in turn is transformed in morphine-3-glucuronide (M3G), an inactive metabolite, and morphine-6-glucuronide (M6G), a potent mu-opioid receptor (MOR) agonist. We have found that heroin addicts exhibit higher M6G/M3G ratios relative to morphine-treated control subjects. We have also shown that heroin-treated rats exhibit measurable levels of M6G (which is usually undetectable in this species) and reduced levels of M3G. Objective We investigated the role of MOR in these effects of heroin, by examining the effects of methadone, a MOR agonist, and of naltrexone, a MOR antagonist, on morphine glucuronidation. We also investigated the effects of alcohol, which is known to alter drug metabolism and is frequently coabused by heroin addicts. Methods Morphine glucuronidation was studied in liver microsomes obtained from rats exposed daily for 10 days to saline, heroin (10 mg/kg, i.p.), naltrexone (20–40 mg/kg, i.p.), heroin + naltrexone (10 mg/kg+20–40 mg/kg, i.p.), methadone (5–20 mg/kg, i.p.), or 10% ethanol. Results Heroin induced the synthesis of M6G and decreased the synthesis of M3G. Naltrexone exhibited intrinsic modulatory activity on morphine glucuronidation, increasing the synthesis of M3G via a low-affinity/high-capacity reaction characterized by positive cooperativity. The rate of M3G synthesis in the heroin + naltrexone groups was not different from that of the naltrexone groups. Methadone and ethanol induced a modest increase in M3G synthesis and had no effect on M6G synthesis. Conclusion The effects of heroin on morphine glucuronidation are not shared by methadone or alcohol (two drugs that figure prominently in the natural history of heroin addiction) and do not appear to depend on the activation of MOR.     

Heroin purity and composition in Sydney, Australia

The aim of the study was to provide baseline data on the pharmacological properties of heroin available for retail sale in Cabramatta, Sydney. A retrospective sampling frame was constructed consisting of all suspected heroin seizures in Cabramatta between October 1996 and March 1997 ( n = 487). A total of 33 street-level 'exhibits', comprising 88 samples, were selected. Ion chromatography was used to determine whether heroin was present as the free base or as the hydrochloride (or other salt). High performance liquid chromatography with diode array detection was used to assess the presence of diacetylmorphine hydrochloride (heroin hydrochloride), O-6-monoacetylmorphine hydrochloride (degradation product) and acetylcodeine hydrochloride (synthesis byproduct). Gas chromatography/mass spectrometry and high performance liquid chromotography with refractive index detection were used to detect adulterants and diluents. All samples contained heroin as the hydrochloride salt. No heroin free base was encountered. The mean purity was 66% with 85% of samples having an average purity of at least 50%. The samples were free of harmful adulterants. Adulterants detected were pharmacologically inactive diluents largely used to add bulk (sugars) or pharmacologically active adulterants used to improve the bioavailability of heroin HCL when smoked (caffeine). Results have implications for attempts to reduce drug-related harms and, in particular, suggest that interventions designed to facilitate transitions from heroin injecting to smoking require careful consideration of the pharmacological factors associated with route of administration.     

Levels of heroin and its metabolites in blood and brain extracellular fluid after i.v. heroin administration to freely moving rats

BACKGROUND AND PURPOSE

Heroin, with low affinity for μ-opioid receptors, has been considered to act as a prodrug. In order to study the pharmacokinetics of heroin and its active metabolites after i.v. administration, we gave a bolus injection of heroin to rats and measured the concentration of heroin and its metabolites in blood and brain extracellular fluid (ECF).

EXPERIMENTAL APPROACH

After an i.v. bolus injection of heroin to freely moving Sprague–Dawley rats, the concentrations of heroin and metabolites in blood samples from the vena jugularis and in microdialysis samples from striatal brain ECF were measured by ultraperformance LC-MS/MS.

KEY RESULTS

Heroin levels decreased very fast, both in blood and brain ECF, and could not be detected after 18 and 10 min respectively. 6-Monoacetylmorphine (6-MAM) increased very rapidly, reaching its maximal concentrations after 2.0 and 4.3 min, respectively, and falling thereafter. Morphine increased very slowly, reaching its maximal levels, which were six times lower than the highest 6-MAM concentrations, after 12.6 and 21.3 min, with a very slow decline during the rest of the experiment and only surpassing 6-MAM levels at least 30 min after injection.

CONCLUSIONS AND IMPLICATIONS

After an i.v. heroin injection, 6-MAM was the predominant opioid present shortly after injection and during the first 30 min, not only in the blood but also in rat brain ECF. 6-MAM might therefore mediate most of the effects observed shortly after heroin intake, and this finding questions the general assumption that morphine is the main and most important metabolite of heroin.     

The history of heroin

The discovery of heroin and the development of heroin abuse are introduced. Heroin, the hydrochloride of diacetylmorphine, was discovered by acetylation of morphine. Heroin, in pharmacological studies, proved to be more effective than morphine or codeine. The Bayer Company started the production of heroin in 1898 on a commercial scale. The first clinical results were so promising that heroin was considered a wonder drug. Indeed, heroin was more effective than codeine in respiratory diseases. It has turned out, however, that repeated administration of heroin results in the development of tolerance and the patients become heroin-addicts soon. In the early 1910s morphine addicts "discovered" the euphorising properties of heroin and this effect was enhanced by intravenous administration. Heroin became a narcotic drug and its abuse began to spread quickly. Restrictions on its production, use and distribution were regulated by international treties. The total ban on heroin production was also proposed. As a result of the strict regulations the production and cosumption of heroin showed a significant decrease after 1931. At the same time the underworld recognized the shortage of heroin and started the illicit production and trafficking. The quantity of heroin seized by law enforcement agencies in the past decades rose gradually. As an indicator of the worldwide heroin market, the quantity of confiscated heroin underwent a tenfold increase since 1970. The paper surveys the most important heroin-producing and trafficking countries. Heroin, prepared in clandestine ("kitchen" or "jungle") laboratories, is diluted ("cut") by every member of the illegal heroin distributing chain, i.e. smugglers, traffickers, dealers and vendors.     

海洛因依赖者防御方式及个性的研究

目的 :了解海洛因依赖者个性、防御方式的特点及两者关系。方法 :采用艾森克个性问卷 (EPQ)及防御方式问卷 (DSQ)对 2 2 8例海洛因依赖者进行自评测试 ,作典型相关分析 ,并与 5 18名高中生的防御方式以及EPQ常模进行对比分析。结果 :海洛因依赖者无论在个性及防御方式方面都存在缺陷 ,而其个性与防御方式又存在较复杂的相关关系。结论 :提示在对吸毒者实行心理干预时 ,应从多方面着手 ,既要改变其防御机制的缺陷 ,促进心理健康 ,又要重建人格与行为模式     

Perceived family environments among ethnic groups of compulsive heroin users.

Predictions that both personality and environmental factors are implicated in heroin addiction were explored with personality measures operationalized by the Minnesota Multiphasic Personality Inventory (MMPI) and by family social climate measures operationalized by the Family Environment Scales (Moos et al., 1974). Hypotheses were supported. Heroin addicts differed appreciably in personality from normative data (Psychopathic deviate, the highest clinical scale; Family Problems, the highest content scale). Heroin users deviated significantly from normative samples in retrospective views of both their past and present family environments (significantly higher Achievement Orientation, Moral-Religious Emphasis, and Organization, contrasted by significantly lower Intellectual-Cultural and Active Recreational Orientations). White heroin users (n = 39) evidenced greater deviance in both personality and family environment than black heroin users (n = 63). Comparisons with Mexican-American heroin users, white polydrug users, and nondrug-abusing comparison groups indicated that, for many addicts, compulsive heroin use is associated with social nonconformity in personality that may be a reaction against family demands for achievement without sufficient modeling of instrumental role skills.