General information about smoked heroin.

Fråga: General information about smoked heroin.

Sammanfattning: Smoking heroin has increased in popularity over the last few years as it offers certain advantages to the user compared with other forms of administration. However, this route of administration can be hazardous to the drug user. A number of cases of leukoencephalopathy have been reported in connection with heroin smoking, attributed to pyrolysis products formed when the drug and other compounds decompose upon heating, although it is difficult to identify the factor causing the toxicity.

Svar: Heroin, or diacetylmorphine or diamorphine, is a semi-synthetic narcotic analgesic which is synthesised from morphine by the acetylation of the phenolic and alcoholic hydroxyl groups. Heroin was originally synthesised from morphine in 1874 and was commercially introduced by the Bayer Company in 1898. An epidemic of heroin use was noted in the early 1970s and illicit use continues to increase.

Heroin is manufactured primarily in South East Asia, Turkey, Pakistan, India, Iran and Nigeria. Illicit heroin is produced by the acetylation of raw opium or purified morphine, and thus may contain other opium alkaloids including acetylmorphine, codeine and papaverine. Illicit heroin may also be mixed with bulk diluents such as mannitol, dextrose, lactose, talc and baking soda. Heroin for smoking is often diluted with a barbiturate or caffeine and sometimes small amounts of strychnine (1). Other compounds found in illicit heroin are for example amphetamine, boric acid, lidocaine, paracetamol, phenobarbital, procaine and quinine.

Heroin is usually self-administered parentally, either by intravenous or subcutaneous injection, but may also be snorted or smoked. In addition, other less common routes of administration include oral, sublingual and rectal.

Heroin is rapidly metabolised in the blood by d-acetylation to 6-acetylmorphine (t1/2 < 10 minutes), after which 6-acetylmorphine is hydrolysed to morphine (t1/2 < 45 minutes). Heroin and 6-acetylmorphine are rapidly distributed to the central nervous system. Morphine is further metabolised by conjugation to morphine glucuronide.

The pharmacological response to heroin is due to the combined effects of its active metabolites, 6-acetylmorphine and morphine, since heroin has little or no affinity for the opiate receptor in the brain. Therefore, it seems likely that heroin serves as a lipid soluble prodrug which facilitates entry of morphine into the central nervous system (2). Both heroin and 6-acetylmorphine readily cross the blood-brain barrier (3).

Heroin elicits its primary pharmacological effects from the central nervous system (euphoria, anaesthesia, analgesia and increased tolerance of pain, stimulation of chemotrigger zone, production of miosis), respiratory system (depression of respiratory rate, volume and exchange and decreased respiratory responsiveness), cardiovascular system (orthostatic hypotension) and gastrointestinal system (decreased motility). Tolerance to analgesia, euphoria and respiratory depression develop rapidly, and physical addiction after repeated use occurs. In acute heroin poisoning, death results from respiratory depression, cardiac arrhythmia due to secondary effects from hypoxia and pulmonary oedema. Anaphylactic shock can also an occur.

Heroin is more potent, has a faster onset of action and a shorter duration of action than morphine. In addition, heroin is more water soluble than morphine, thus smaller injection volumes are possible (2,3). In some documents it has been reported that heroin produces less nausea, vomiting, constipation and hypotension (2,3) and in other documents adverse effects have been reported to increase compared with morphine. However, heroin has no medical field of application. No better effect compared with morphine has been reported.

The detection of heroin in biological samples is very difficult since the plasma half-life is short. In addition, heroin is not stable in solution. Therefore, routine toxicological analysis of specimens usually employs identification and quantitation of free and conjugated morphine in blood and urine (2). Morphine and morphine glucuronide are the main excretion products in the urine (3). In addition, identification of 6-acetylmorphine in blood and urine may be used to document previous heroin use (2).

Smoking the drug offers certain advantages to the user. Purity of the drug is less important for smoking than it is for intravenous use (4). This route of administration is simple, facilitates rapid absorption and results in rapid delivery of inhaled substances to the central nervous system (1). As drug users become aware of the dangers of AIDS associated with intravenous drug use, it is possible that smoking will increase in popularity as a means of drug taking.

However, smoking drugs presents added hazards to the drug user. Many organic compounds undergo pyrolytic or oxidative reactions when exposed to high temperatures in the presence of air. The resulting compounds may have acute toxicities differing from those of the parent drug, as well as having more long-term effects, such as the induction of lung cancer associated with tobacco smoking (4).

Opium has been smoked for centuries in the Middle and Far East. Therefore, when in the early 1900s heroin was introduced in China and started replacing opium as a narcotic, it was also usually smoked (4). The earliest scientific study of the bioavailability of heroin by this route was reported in 1937. In 1966 Mou and Way (cited in reference 1) found that 14 per cent of the dose of heroin smoked in cigarettes could be recovered in urine as morphine (conjugated and free), whereas a 25 per cent morphine recovery was achieved in urine after "dragon chasing" (inhalation of smoke from heroin heated on aluminium foil (4)) compared with the recovery of 68 per cent of an iv dose of heroin as morphine. This would give a bioavailability of 21 per cent for smoking of cigarettes and 37 per cent for dragon chasing (1).

A number of cases of leukoencephalopathy have been attributed to a toxic compound or compounds obtained from heroin smoking but no specific compound has yet been implicated (4). Significant amounts of the drug are decomposed on heating. Cook and Brine (1985; cited in reference 1) studied the pyrolysis products of both heroin and heroin hydrochloride. They identified heroin and 3 major pyrolysis products in the 250 degree pyrolysate of heroin hydrochloride. The products were 6-0-acetylmorphine, N,6-diacetylnormorphine, and N,3-0,6-0-triacetylnormorphine. In addition, a minor component was suggested to be 3,4-diacetoxyphenanthrene. Formation of this compound illustrates the extensive breakdown that can occur under pyrolytic conditions (1).

When heroin hydrochloride was heated on aluminium foil (Huizer 1987; cited from referebce 1), the aforementioned major products reported by Cook and Brine were found in the residue. The amounts of these products increased with increasing temperature. Heroin base gave smaller amounts of pyrolysis products, with 6-0-acetylmorphine predominating. Caffeine enhanced the volatilisation and changed the ratio of products to favour 6-0-acetylmorphine. Thus, caffeine has a very strong positive effect on the volatilisation of heroin hydrochloride, as does barbital, whereas ascorbic acid markedly reduced the amount of the drug in the smoke. Recoveries of heroin in the fumes from heating on aluminium foil ranged from nearly 80 per cent for the free base mixed with caffeine to about one per cent when ascorbic acid was used as the diluent. Thus, the amount of heroin inhaled by smoking is strongly dependent on the presence of diluents, and these also may influence the ratio of pyrolysis products obtained (1).

Since a large number of other compounds are apparently produced in minor amounts when heroin is heated, and since diluents used in street samples may also undergo pyrolysis to potentially toxic products, it appears that the smoking of heroin could have significant toxicological consequences (4). Further information on the pharmacological and toxicological implications of this type of heroin administration is needed.