Heroin in Malaysia and Singapore.

Clandestine heroin laboratories have been a feature of the Malaysian illicit drug scene since soon after the abuse of heroin emerged in 1972. The first few clandestine heroin laboratories which synthesised heroin via the acetylation of imported morphine were uncovered in 1973 and 1977. By the mid-1980s, this type of laboratory was replaced by heroin-cutting laboratories whereby imported high-grade heroin was cut to street heroin. This was to meet the rising demand for the drug owing to the rapid escalation of the number of drug users. Over the years, the most significant change in the composition of the street heroin is the decrease in its purity from 30%-50% to 3%-5%. Caffeine has remained the major adulterant and chloroquine is detected in virtually all recent seizures.

A scoping review of home-produced heroin and amphetamine-type stimulant substitutes: implications for prevention, treatment, and policy.

Several home-produced substances such as krokodil and boltushka are prevalent in many Eastern European countries. Anecdotal reports of its use have been circulating in Germany and Norway; however, this has not been confirmed. Its use has also been reported by the media in the USA, although only one confirmed report of its use exists. Home-produced drugs are associated with high levels of morbidity and a number of complex health issues such as the spread of blood borne viruses, gangrene, and internal organ damage. The high incidence of HIV rates amongst people who inject home-produced substances is a public health concern. The resulting physical health consequences of injecting these crude substances are very severe in comparison to heroin or amphetamine acquired in black markets. Due to this fact and the increased mortality associated with these substances, professionals in the area of prevention, treatment, and policy development need to be cognisant of the presentation, harms, and the dangers associated with home-produced substances globally. This scoping review aimed to examine existing literature on the subject of home-produced heroin and amphetamine-type stimulant substitutes. The review discussed the many implications such research may have in the areas of policy and practice. Data were gathered through the use of qualitative secondary resources such as journal articles, reports, reviews, case studies, and media reports. The home production of these substances relies on the utilisation of precursor drugs such as less potent stimulants, tranquillizers, analgesics, and sedatives or natural plant ingredients. The Internet underpins the facilitation of this practice as recipes, and diverted pharmaceutical sales are available widely online, and currently, ease of access to the Internet is evident worldwide. This review highlights the necessity of prevention, education, and also harm reduction related to home-produced drugs and also recommends consistent monitoring of online drug fora, online drug marketplaces, and unregulated pharmacies.

Economical synthesis of 13C-labeled opiates, cocaine derivatives and selected urinary metabolites by derivatization of the natural products.

The illegal use of opiates and cocaine is a challenge world-wide, but some derivatives are also valuable pharmaceuticals. Reference samples of the active ingredients and their metabolites are needed both for controlling administration in the clinic and to detect drugs of abuse. Especially, (13)C-labeled compounds are useful for identification and quantification purposes by mass spectroscopic techniques, potentially increasing accuracy by minimizing ion alteration/suppression effects. Thus, the synthesis of [acetyl-(13)C4]heroin, [acetyl-(13)C4-methyl-(13)C]heroin, [acetyl-(13)C2-methyl-(13)C]6-acetylmorphine, [N-methyl-(13)C-O-metyl-(13)C]codeine and phenyl-(13)C6-labeled derivatives of cocaine, benzoylecgonine, norcocaine and cocaethylene was undertaken to provide such reference materials. The synthetic work has focused on identifying (13)C atom-efficient routes towards these derivatives. Therefore, the (13)C-labeled opiates and cocaine derivatives were made from the corresponding natural products.

Clostridium botulinum: an increasing complication of heroin misuse.

Wound botulism is a rare infectious disease due to neurotoxin release from the anaerobic, spore-forming bacterium Clostridium botulinum that is becoming an ever more frequent complication of parenteral drug abuse in the Western world. Before the year 2000, no such cases had been reported in the UK and Ireland, but since then the number of proven and suspected cases of wound botulism occurring in parenteral drug users has increased markedly. The diagnosis is often difficult, based on a high degree of clinical suspicion and if not considered in the initial differential diagnosis, then considerable delays in treatment may result. This is the case report of a male heroin user who presented three times to an Emergency Department in the UK before a diagnosis of wound botulism was made and treatment commenced. It is important that emergency clinicians are aware of the possibility of wound botulism in parenteral drug users that present with unusual neurological or respiratory symptomatology.

La inyección de drogas en Bogotá: una amenaza creciente / Drug injection in Bogotá: a growing threat

Este proyecto hace parte de la Fase II del estudio mundial sobre Uso de Drogas Inyectadas y Riesgos para la salud de la Organización Mundial de la Salud. Esta fase de la investigación debía proveer información acerca de la naturaleza actual, extensión e implicaciones del uso intravenoso de drogas, así como una mejor comprensión de los factores socio-culturales que podrían estar influenciando la toma de riesgos. Se entrevistaron 410 personas en la ciudad de Bogotá, Colombia, (inyectores, ex-inyectores, expendedores y no inyectores). Las personas fueron contactadas inicialmente en su ambiente natural y posteriormente en recintos privados para la realización de grupos focales. Los resultados sugieren que el uso intravenoso de drogas es más frecuente de lo que se pensaba; los riesgos del policonsumo de drogas, del uso intravenoso de éstas, de la actividad sexual desprotegida, evidencian que la población de inyectores es un foco importante para el desarrollo de epidemias como el VIH y la Hepatitis B y C. La realidad del uso intravenoso de drogas es un problema que ha permanecido "oculto" y las consecuencias para la salud de los inyectores no han sido del todo evidentes hasta ahora. El potencial de una difusión continuada de la práctica entre redes de consumidores en la ciudad y las consecuencias que de ello se derivarían, deberán ser contempladas por quienes construyen políticas, ofrecen servicios y diseñan intervenciones

This Project is part of Phase II of the WHO Injected Drug Use and Health Risks worldwide study. The objective was to obtain information on the current nature, extension and implications of injected drug use, in addition to gaining a better understanding of the socio-cultural factors that could influence risk taking. 410 people were interviewed in a sample drawn from Bogóta, Colombia (injectors, former injectors, dealers and non-injectors). SubjBcts were initially contacted in their natural environment and met, subsequently, on private premises for focal groups. Results show that drug injection is more common than previously assumed. Risk behaviours associated with multidrug use, injecting these, and unsafe sex suggest that this population of injectors is a significant source for epidemics such as HIV and hepatitis B and C. The reality of intravenous drug use has been "hidden" and its consequences on the health of those who inject have not been apparent upto now. The potential for a continual spread of such a practice among user networks in the city and the repercussion deriving from this must be taken into consideration by policymakers in implementing services and drawing up interventions

Documentation of a heroin manufacturing process in Afghanistan.

The present article documents an authentic process of heroin manufacturing in Afghanistan: white heroin hydrochloride produced using simple equipment and a small quantity of chemicals. The quantities of chemicals actually used corresponded to the minimum needed for manufacturing heroin. The only organic solvent used was acetone, and only a very small quantity of it was used. Because the chemicals used in the demonstration were from actual seizures in Afghanistan, some of the chemicals had been disguised or repackaged by smugglers. Others had been put into labelled containers that proved to be counterfeit, and some glass containers used were not the original containers of the manufacturer displayed on the label. The brown heroin base prepared as an intermediate step in the process shares some of the characteristics of the South-West Asia type of heroin preparations often seized in Germany. The final product of the documented heroin manufacturing process was white heroin hydrochloride, which shares the key characteristics of the white heroin occasionally seized in Germany and other countries in Western Europe since 2000. The present article demonstrates that this kind of heroin can be produced in Afghanistan.

Drug profiling: a new scientific contribution to law enforcement operations in Viet Nam.

Since 1995 heroin sample comparisons have been carried out in Viet Nam to establish links between wholesalers and retailers. To that end, the physical and chemical characteristics of samples are analysed: their colour, the packaging material, including fingerprints, diacetylmorphine (heroin) content and the composition of some main alkaloids. At the beginning of 2002, having acquired expertise on impurity profiling and with the support of new instruments, the Institute of Forensic Sciences of Viet Nam introduced the routine impurity profiling of seized heroin and methamphetamine and later undertook to explain that process to national law enforcement bodies. Since then, 375 heroin and 29 methamphetamine samples have been analysed for major and minor impurities. Substances detected in the analysis of illicit heroin include diacetylmorphine, morphine, codeine, 06-monoacetylmorphine and acetylcodeine as well as adulterants such as paracetamol and caffeine. Since methamphetamine impurity profiling began, 29 samples have so far been analysed, and some samples have been grouped through the application of cluster analysis. In the case of heroin, impurity profiling has established a link between two major trafficking groups suspected of obtaining heroin from the same source of production. Analysis has also revealed a link between one wholesaler and several retailers in one region. In addition, impurity profiling provides new information on the preparation and production of some methamphetamine and fake Ecstasy tablets.

Process characterisation, optimisation and validation of production of diacetylmorphine/caffeine sachets: a design of experiments approach.

Powder filled sachets containing a 3:1 (w/w) powder mixture of diacetylmorphine base and caffeine anhydrate were developed as a dosage form for smokable heroin used for the treatment of chronic, treatment-resistant heroin addicts. The powder mixture was filled into sachets using a micro dose auger filler machine. The goal of this study was to identify the most important process variables that influence precision of dosing. Five variables were tested: auger speed, agitator speed, hopper fill level, dose interval, and dose. An experimental design was used to study the effects of each of these variables, including possible non-linear and interaction effects. A 9-term regression model was constructed, explaining 94% of the observed variation in dose weight variation coefficient. Dose, agitator speed and hopper fill level were the most important variables. The regression model was used to identify optimal settings of the variables for four sachet doses intended for routine manufacture. The results of four test batches manufactured with these optimised settings showed that accurate (accuracy: 99.0-101.0%) and precise (CV: 3.2-5.3%) filling of diacetylmorphine/caffeine sachets is possible using the micro dose auger filler machine.

Pharmaceutical development of an intravenous dosage form of diacetylmorphine hydrochloride.

A solid dosage form for multiple use was developed for parenteral administration of diacetylmorphine in a clinical trial on co-prescription of heroin to heroin addicts. A 300-mg/mL diacetylmorphine hydrochloride solution was lyophilised as 10-mL aliquots in 30-mL glass vials, to be reconstituted to 150 mg/mL with water for injection before use. Addition of bulking agents for improvement of the cake structure of the lyophilised product appeared unnecessary. Stability studies indicated good stability of the lyophilised product under prescribed storage conditions (25 degrees C, 60% relative humidity) and under more extreme conditions (40 degrees C, 75% relative humidity). The reconstituted product was found to be stable for six days at room temperature. Suitability of the product for multiple use was supported by the fact that the reconstituted product was found to be antimicrobially active.

Acetylcodeine, an impurity of illicitly manufactured heroin, elicits convulsions, antinociception, and locomotor stimulation in mice.

Acetylcodeine is one of the major impurities present in illicitly manufactured heroin (diacetylmorphine). Data on its pharmacology and toxicology are limited and its ability to alter the toxic effects of diacetylmorphine is not known. The first objective of the present study was to compare the acute pharmacological and toxicological effects of acetylcodeine to those of codeine and diacetylmorphine in mice by assessing nociception in the tail-flick test, locomotor stimulation, and convulsive behavior. The second goal of this study was to determine whether acetylcodeine would alter the convulsant effects of diacetylmorphine. The antinociceptive potencies of acetylcodeine and codeine were similar, as reflected by their ED50 (95% confidence limits) values of 35 (29-44) and 51 (40-65) micromol/kg, respectively. Acetylcodeine was somewhat less potent than codeine in stimulating locomotor behavior, with ED50 values of 28 (22-37) and 12 (6-24) micromol/kg, respectively. Diacetylmorphine was considerably more potent than the other two drugs, producing antinociception and locomotor stimulation at ED50 values of 2.4 (1.4-4.1) and 0.65 (0.36-1.2) micromol/kg, respectively. On the other hand, the convulsant effects of acetylcodeine (ED50=138 (121-157) micromol/kg) and diacetylmorphine (ED50=115 (81-163) micromol/kg) were similar in potency and both were more potent than codeine (ED50=231 (188-283) micromol/kg). Finally, a subthreshold dose of acetylcodeine (72 micromol/kg) decreased the convulsant ED50 dose of diacetylmorphine to 40 (32-49). These findings suggest that the convulsant effects of acetylcodeine are more potent than predicted by its effects on locomotor activity and antinociception. The observation that acetylcodeine potentiated the convulsant effects of diacetylmorphine suggests a mechanism for some of the heroin-related deaths reported in human addicts.

Formation of O-6-acetylmorphine in the 'homebake' preparation of heroin.

When O-6-acetylmorphine is found in toxicological or in illicit drugs cases it is usually assumed to be the product of heroin degradation. It is, therefore, used as evidence for the prior existence of heroin. In this study, it was found that, when morphine is partly acetylated with acetyl chloride, O-6-acetylmorphine is produced. In some experiments, partial acetylation of morphine sulphate yielded mixtures which contained O-6-acetylmorphine, unreacted morphine and only traces of O-3-acetylmorphine and heroin. Therefore, in cases where O-6-acetylmorphine is found in the absence of heroin, it should not be used as evidence of heroin having been present.

Analytical characterization of isoheroin.

The synthesis of isoheroin is presented with the analytical data (mass spectroscopy [MS], nuclear magnetic resonance [NMR], infrared spectroscopy [IR], and gas liquid chromatography [GLC]) for this compound. Comparison between analytical results for heroin and isoheroin shows differentiation is possible.

Analytical studies on illicit heroin. I. The occurrence of O3-monoacetylmorphine.

A thin-layer chromatographic method and a high pressure liquid chromatographic method have been developed for the analysis of O3-monoacetylmorphine in illicit heroin samples. The possible formation of O3-monoacetylmorphine during the production process of heroin and during its hydrolysis were also studied using these methods.

Chemistry and pharmacology of homologs of 6-acetyl-and 3,6-diacetylmorphine.

3,6-Diformyl- and 3,6-dipropanoylmorphine and 6-formyl- and 6-propanoylmorphine were prepared to obtain longer acting, heroin-like compounds. The 6-acylated compounds were more potent than heroin subcutaneously and were orally effective, and their duration of action was at least two to three times greater than that of heroin in monkey species.

Preparation and analgesic activity of 3,6-diacetylnormorphine and 6-acetylnormorphine.

3,6-Diacetylnormorphine (norheroin) and 6-acetylnormorphine have been prepared in excellent yield through the 3,N-bis(tert-butoxycarbonyl) derivative of normorphine via acetylation and selective removal of protecting groups. This general procedure would be applicable to the preparation of various 3,6-diesters or 6-monoesters of normorphine. The analgesic potency of norheroin was found to be the same as that of 6-acetylnormorphine, about 0.05 that of heroin. The onset, peak, and duration of action of these compounds were nearly identical and comparable with morphine.