Systematic (IUPAC) name | |
---|---|
(5α,6α)-7,8-didehydro- 4,5-epoxy- 17-methylmorphinan- 3,6-diol diacetate | |
Identifiers | |
CAS number | 561-27-3 |
ATC code | N02AA09 |
PubChem | CID 5462328 |
DrugBank | DB01452 |
ChemSpider | 4575379 |
Chemical data | |
Formula | C21H23NO5 |
Mol. mass | 369.41 g/mol |
Synonyms | Diamorphine, Diacetylmorphine, Acetomorphine, (Dual) Acetylated morphine, Morphine diacetate |
Pharmacokinetic data | |
Bioavailability | <35% (oral), 44–61% (inhaled)[1] |
Protein binding | 0% (morphine metabolite 35%) |
Metabolism | hepatic |
Half-life | <10 minutes [1] |
Excretion | 90% renal as glucuronides, rest biliary |
Therapeutic considerations | |
Pregnancy cat. | Category X |
Legal status | Prohibited (S9) (AU) Schedule I (CA) ? (UK) Schedule I (US) |
Dependence liability | Extremely High |
Routes | Inhalation, Transmucosal, Intravenous, Oral, Intranasal, Rectal, Intramuscular |
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Heroin, or diacetylmorphine (INN), also known as diamorphine (BAN), is a semi-synthetic opioid drug synthesized from morphine, a derivative of the opium poppy. It is the 3,6-diacetyl ester of morphine (di (two)-acetyl-morphine). The white crystalline form is commonly the hydrochloride salt diacetylmorphine hydrochloride, though often adulterated thus dulling the sheen and consistency from that to a matte white powder, which heroin freebase typically is.[2] 90% of heroin is said to be produced in Afghanistan.[3]
As with other opioids, heroin is used as both an analgesic and a recreational drug. Frequent and regular administration is associated with tolerance and physical dependence, which may develop into addiction.
Internationally, heroin is controlled under Schedules I and IV of the Single Convention on Narcotic Drugs.[4] It is illegal to manufacture, possess, or sell diacetylmorphine without a license in Belgium, Denmark, Germany, Iran, India, the Netherlands, the United States, Australia, Canada, Ireland, Pakistan, the United Kingdom and Swaziland.
Under the name diamorphine, it is a legally prescribed controlled drug in the United Kingdom. It is available for prescription to long-term users in the Netherlands, United Kingdom, Switzerland, Germany and Denmark alongside psycho-social care,[5][6] and a similar programme is being campaigned for by liberal political parties in Norway. Some countries allow the government to sell or donate high-quality seizures of drugs and precursors which are otherwise legal for medicinal use to pharmaceutical manufacturers for use in preparing licit supplies of medical drugs and research chemicals; this was the case in Croatia prior to 2007.[7]
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The German drug company Bayer named its new over the counter drug "Heroin" in 1895.[8] The name was derived from the German word "heroisch" (heroic) due to its perceived "heroic" effects upon a user.[8] It was chiefly developed as a morphine substitute for cough suppressants that did not have morphine's addictive side-effects. Morphine at the time was a popular recreational drug, and Bayer wished to find a similar but non-addictive substitute to market.[9] However, contrary to Bayer's advertising as a "non-addictive morphine substitute," heroin would soon have one of the highest rates of dependence amongst its users.[10]
The opium poppy was cultivated in lower Mesopotamia as long ago as 3400 BCE.[11] The chemical analysis of opium in the 19th century revealed that most of its activity could be ascribed to two alkaloids, codeine and morphine.
Diacetylmorphine was first synthesized in 1874 by C. R. Alder Wright, an English chemist working at St. Mary's Hospital Medical School in London. He had been experimenting with combining morphine with various acids. He boiled anhydrous morphine alkaloid with acetic anhydride for several hours and produced a more potent, acetylated form of morphine, now called diacetylmorphine. The compound was sent to F. M. Pierce of Owens College in Manchester for analysis. Pierce told Wright:
“ | Doses ... were subcutaneously injected into young dogs and rabbits ... with the following general results ... great prostration, fear, and sleepiness speedily following the administration, the eyes being sensitive, and pupils constrict, considerable salivation being produced in dogs, and slight tendency to vomiting in some cases, but no actual emesis. Respiration was at first quickened, but subsequently reduced, and the heart's action was diminished, and rendered irregular. Marked want of coordinating power over the muscular movements, and loss of power in the pelvis and hind limbs, together with a diminution of temperature in the rectum of about 4°.[12] | ” |
Wright's invention did not lead to any further developments, and diacetylmorphine only became popular after it was independently re-synthesized 23 years later by another chemist, Felix Hoffmann. Hoffmann, working at the Aktiengesellschaft Farbenfabriken (today the Bayer pharmaceutical company) in Elberfeld, Germany, was instructed by his supervisor Heinrich Dreser to acetylate morphine with the objective of producing codeine, a constituent of the opium poppy, pharmacologically similar to morphine but less potent and less addictive. Instead the experiment produced an acetylated form of morphine one and a half to two times more potent than morphine itself.
From 1898 through to 1910 diacetylmorphine was marketed under the trade name Heroin as a non-addictive morphine substitute and cough suppressant. Bayer marketed the drug as a cure for morphine addiction before it was discovered that it rapidly metabolizes into morphine. As such, heroin is essentially a quicker acting form of morphine. The company was embarrassed by the new finding, which became a historic blunder for Bayer.[13]
In the U.S.A. the Harrison Narcotics Tax Act was passed in 1914 to control the sale and distribution of "heroin" and other opioids, which allowed the drug to be prescribed and sold for medical purposes. In 1924 the United States Congress banned its sale, importation or manufacture. It is now a Schedule I substance, which makes it illegal for non-medical use in signatory nations of the Single Convention on Narcotic Drugs treaty, including the United States.
The Health Committee of the League of Nations banned heroin in 1925 although it took more than three years for this to be implemented. In the meantime, the first designer drugs, viz. 3,6 diesters and 6 monoesters of morphine and acetylated analogues of closely-related drugs like hydromorphone and dihydromorphine were produced in massive quantities to fill the worldwide demand for heroin -- this continued until 1930 when the Committee banned heroin analogues with no therapeutic advantage over drugs already in use, the first major legislation of this type.[14]
Later, as with Aspirin, Bayer lost some of its trademark rights to "heroin" under the 1919 Treaty of Versailles following the German defeat in World War I.[15]
When taken orally, diacetylmorphine undergoes extensive first-pass metabolism via deacetylation, making it a prodrug for the systemic delivery of morphine.[16] When the drug is injected, however, it avoids this first-pass effect, very rapidly crossing the blood-brain barrier due to the presence of the acetyl groups, which render it much more lipid-soluble than morphine itself.[17] Once in the brain, it then is deacetylated variously into the inactive 3-monoacetylmorphine and the active 6-monoacetylmorphine (6-MAM), and then to morphine which bind to μ-opioid receptors, resulting in the drug's euphoric, analgesic (pain relief), and anxiolytic (anti-anxiety) effects; diacetylmorphine itself exhibits relatively low affinity for the μ receptor.[18] Unlike hydromorphone and oxymorphone, however, administered intravenously, diacetylmorphine creates a larger histamine release, similar to morphine, resulting in the feeling of a greater subjective "body high" to some, but also instances of pruritus (itching) when they first start using.[19]
Both morphine and 6-MAM are μ-opioid agonists which bind to receptors present throughout the brain, spinal cord and gut of all mammals. The μ-opioid receptor also binds endogenous opioid peptides such as β-endorphin, Leu-enkephalin, and Met-enkephalin. Repeated use of diacetylmorphine results in a number of physiological changes, including decreases in the number of μ-opioid receptors. These physiological alterations lead to tolerance and dependence, so that cessation of diacetylmorphine use results in a set of remarkably uncomfortable symptoms including pain, anxiety, muscle spasms, and insomnia called the opioid withdrawal syndrome. Depending on usage it has an onset four to 24 hours after the last dose of diacetylmorphine. Morphine also binds to δ- and κ-opioid receptors.
There is also evidence that 6-MAM binds to a subtype of μ-opioid receptors which are also activated by the morphine metabolite morphine-6β-glucuronide but not morphine itself.[20] The third substype of third opioid type (mu-3) receptor. Which may be a commonality to other six position monoesters of morphine. The contribution of these receptors to the overall pharmacology of heroin remains unknown.
A subclass of morphine derivatives, namely the 3,6 esters of morphine, with similar effects and uses includes the clinically-used strong analgesics nicomorphine (Vilan), and dipropanoylmorphine; there is also the latter's dihydromorphine analogue, diacetyldihydromorphine (Paralaudin). Two other 3,6 diesters of morphine invented in 1874-5 along with heroin, dibenzoylmorphine and acetylpropionylmorphine, were made as heroin substitutes after heroin was outlawed in 1925 and therefore sold as the first "designer drugs" until they were outlawed by the League of Nations in 1930.
Worldwide, the UN estimates there are more than 50 million regular users of heroin, cocaine and synthetic drugs.[21] Global users of heroin are estimated at between 15.16 million and 21.13 million people aged 15–64.[22]
Under the name diamorphine, heroin is prescribed as a strong analgesic in the United Kingdom, where it is given via subcutaneous, intramuscular, intrathecal or intravenous route. Its use includes treatment for acute pain, such as in severe physical trauma, myocardial infarction, post-surgical pain, and chronic pain, including end-stage cancer and other terminal illnesses. In other countries it is more common to use morphine or other strong opioids in these situations.
In 2005, there was a shortage of diamorphine in the UK, due to a problem at the main UK manufacturers.[23] Due to this, many hospitals changed to using morphine instead of diamorphine. Although there is no longer a problem with the manufacturing of heroin in the UK, many hospitals there have continued to use morphine.
Diamorphine continues to be widely used in palliative care in the United Kingdom, where it is commonly given by the subcutaneous route, often via a syringe driver, if patients could not easily swallow oral morphine solution. The advantage of diamorphine over morphine is that diamorphine is more soluble and smaller volumes of diamorphine are needed for the same analgesic effect. Both of these factors are advantageous if giving high doses of opioids via the subcutaneous route, which is often necessary in palliative care.
The medical use of diamorphine (in common with other strong opioids such as morphine, fentanyl and oxycodone) is controlled in the United Kingdom by the Misuse of Drugs Act 1971. In the UK, it is a class A controlled drug. Registers of its use are required to be kept in hospitals.
Heroin is also used as a maintenance drug in the treatment of heroin addicts. Though this is somewhat controversial among proponents of a zero tolerance drug policy it has proven superior to methadone in improving the social and health situation of addicts.[24] See: Heroin prescription for addicts
Diacetylmorphine is used as a recreational drug for the transcendent relaxation and intense euphoria it induces. Anthropologist Michael Agar once described heroin as "the perfect whatever drug."[25] Tolerance quickly develops, and users need more of the drug to achieve the same effects. Its popularity with recreational drug users, compared to morphine, reportedly stems from its perceived different effects.[26] In particular, users report an intense rush that occurs while the diacetylmorphine is being metabolized into 6-monoacetylmorphine (6-MAM) and morphine in the brain. Diacetylmorphine produces more euphoria than other opioids upon injection. One possible explanation is the presence of 6-monoacetylmorphine, a metabolite unique to diacetylmorphine. While other opioids of recreational use, such as codeine, produce only morphine, heroin also leaves 6-MAM, also a psycho-active metabolite. However, this perception is not supported by the results of clinical studies comparing the physiological and subjective effects of injected diacetylmorphine and morphine in individuals formerly addicted to opioids; these subjects showed no preference for one drug over the other. Equipotent injected doses had comparable action courses, with no difference in subjects' self-rated feelings of euphoria, ambition, nervousness, relaxation, drowsiness, or sleepiness.[27]
Short-term addiction studies by the same researchers demonstrated that tolerance developed at a similar rate to both diacetylmorphine and morphine. When compared to the opioids hydromorphone, fentanyl, oxycodone, and pethidine/meperidine, former addicts showed a strong preference for diacetylmorphine and morphine, suggesting that diacetylmorphine and morphine are particularly susceptible to abuse and addiction. Morphine and diacetylmorphine were also much more likely to produce euphoria and other positive subjective effects when compared to these other opioids.[27]
One of the most common methods of illicit heroin use is via intravenous injection (colloquially termed "slamming" or "shooting up"). Heroin base (commonly found in Europe), when prepared for injection will only dissolve in water when mixed with an acid (most commonly citric acid powder or lemon juice) and heated. Heroin in the US is most commonly found in the hydrochloride salt form, requiring just water to dissolve. Users tend to initially inject in the easily accessible arm veins, but as these veins collapse over time, through damage caused by the acid, the user will often resort to injecting in other veins.
Recreational users may also administer the drug through snorting, or smoking by inhaling its vapors when heated; either with tobacco in a rolled cigarette or by heating the drug on aluminium foil from underneath.[29] When heated the heroin powder changes to a thick liquid, similar in consistency to molten wax, and it will run across the foil giving off smoke which the user inhales through a tube, usually made from foil also so that any heroin that collects on the inside of the tube can be smoked afterward. This method of administration is known as chasing the dragon (whereas smoking methamphetamine is known as "chasing the white dragon").
The diacetylmorphine dose used for recreational purposes is dependant on the frequency and level of use. A first-time user may ingest between 5 and 20 mg of diacetylmorphine, while an addict may require several hundred mg per day.[30]
The onset of diacetylmorphine's effects depends upon the route of administration. Studies have shown that the subjective pleasure of drug use (the reinforcing component of addiction) is proportional to the rate at which the blood level of the drug increases.[31] Intravenous injection provides the fastest and most intense rush[32] within seven to eight seconds. Intra-muscular injection produces a relatively slow onset of five to eight minutes. Snorting or smoking reaches peak effects within 10 to 15 minutes.[33] If taken orally, the effects take approximately half an hour to set in, with an absence of a rush.
Large doses of heroin can cause fatal respiratory depression, and the drug has been used for suicide or as a murder weapon. The serial killer Dr Harold Shipman used it on his victims, as did Dr John Bodkin Adams (see his victim: Edith Alice Morrell).
Because significant tolerance to respiratory depression develops quickly with continued use and is lost just as quickly during withdrawal, it is often difficult to determine whether a heroin death was an accident, suicide or murder. Examples include the overdose deaths of Sid Vicious, Janis Joplin, Tim Buckley, Layne Staley, Bradley Nowell, Ted Binion, and River Phoenix.[35]
Chronic opioid use, such as heroin, has potentially been shown to be a cause of hyponatremia, resultant due to excess vasopressin secretion.
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The major metabolites of heroin, 6-MAM, morphine, morphine-3-glucuronide and morphine-6-glucuronide, may be quantitated in blood, plasma or urine to monitor for abuse, confirm a diagnosis of poisoning or assist in a medicolegal death investigation. Most commercial opiate screening tests cross-react appreciably with these metabolites, as well as with other biotransformation products likely to be present following usage of street-grade heroin such as 6-acetylcodeine and codeine. However, chromatographic techniques can easily distinguish and measure each of these substances. When interpreting the results of a test, it is important to consider the heroin usage history of the individual, since a chronic user can develop tolerance to doses that would incapacitate an opiate-naive individual, and the chronic user often has high baseline values of these metabolites in his system. Furthermore, some testing procedures employ a hydrolysis step prior to quantitation that converts many of the metabolic products to morphine, yielding a result that may be many times larger than with a method that examines each product individually.[36]
In the Netherlands, diamorphine (heroin) is a List I drug of the Opium Law. It is available for prescription under tight regulation to long-term heroin addicts for whom methadone maintenance treatment has failed. Heroin is exclusively available for prescription to long-term heroin addicts, and cannot be used to treat severe pain or other illnesses.
In the United States, heroin is a schedule I drug according to the Controlled Substances Act of 1970, making it illegal to possess without a DEA license. Possession of more than 100 grams of heroin or a mixture containing heroin is punishable with a minimum mandatory sentence of 5 years of imprisonment in a federal prison.
In Canada, heroin is a controlled substance under Schedule I of the Controlled Drugs and Substances Act (CDSA). Any person who seeks or obtains heroin without disclosing authorization 30 days prior to obtaining another prescription from a practitioner is guilty of an indictable offense and subject to imprisonment for a term not exceeding seven years. Possession of heroin for the purpose of trafficking is guilty of an indictable offense and subject to imprisonment for life.
In Hong Kong, heroin is regulated under Schedule 1 of Hong Kong's Chapter 134 Dangerous Drugs Ordinance. It is available by prescription. Anyone who supplies heroin without a valid prescription can be fined $10,000 (HKD). The penalty for trafficking or manufacturing heroin is a $5,000,000 (HKD) fine and life imprisonment. Possession of heroin without a license from the Department of Health is illegal with a $1,000,000 (HKD) fine and/or 7 years of jail time.
In the United Kingdom, heroin is available by prescription, though it is a restricted Class A drug. According to the 50th edition of the British National Formulary (BNF), diamorphine hydrochloride may be used in the treatment of acute pain, myocardial infarction, acute pulmonary oedema, and chronic pain. The treatment of chronic non-malignant pain must be supervised by a specialist. The BNF notes that all opioid analgesics cause dependence and tolerance but that this is "no deterrent in the control of pain in terminal illness". When used in the palliative care of cancer patients, heroin is often injected using a syringe driver.
The European Monitoring Centre for Drugs and Drug Addiction reports that the retail price of brown heroin varies from €14.5 per gram in Turkey to €110 per gram in Sweden, with most European countries reporting typical prices of €35-40 per gram. The price of white heroin is reported only by a few European countries and ranged between €27 and €110 per gram.[37]
The United Nations Office on Drugs and Crime claims in its 2008 World Drug Report that typical US retail prices are US$172 per gram.[38]
Heroin, also known as diacetyl morphine is produced from acetylation of morphine derived from natural opium sources. Numerous mechanical and chemical means are used to purify the final product. The final products have different appearance depending on purity and have different names.[39]
The origins of the present international illegal heroin trade can be traced back to laws passed in many countries in the early 1900s that closely regulated the production and sale of opium and its derivatives including heroin. At first, heroin flowed from countries where it was still legal into countries where it was no longer legal. By the mid-1920s, heroin production had been made illegal in many parts of the world. An illegal trade developed at that time between heroin labs in China (mostly in Shanghai and Tianjin) and other nations. The weakness of government in China and conditions of civil war enabled heroin production to take root there. Chinese triad gangs eventually came to play a major role in the heroin trade. The French Connection route started in the 1930s.
Heroin trafficking was virtually eliminated in the U.S. during World War II due to temporary trade disruptions caused by the war. Japan's war with China had cut the normal distribution routes for heroin and the war had generally disrupted the movement of opium.
After World War II, the Mafia took advantage of the weakness of the postwar Italian government and set up heroin labs in Sicily. The Mafia took advantage of Sicily's location along the historic route opium took westward into Europe and the United States.[40]
Large scale international heroin production effectively ended in China with the victory of the communists in the civil war in the late 1940s. The elimination of Chinese production happened at the same time that Sicily's role in the trade developed.
Although it remained legal in some countries until after World War II, health risks, addiction, and widespread recreational use led most western countries to declare heroin a controlled substance by the latter half of the 20th century.
In late 1960s and early 70s, the CIA supported anti-Communist Chinese Nationalists settled near Sino-Burmese border and Hmong tribesmen in Laos. This helped the development of the Golden Triangle opium production region, which supplied about one-third of heroin consumed in US after 1973 American withdrawal from Vietnam. As of 1999, Myanmar (formerly Burma), the heartland of the Golden Triangle remained the second largest producer of heroin, after Afghanistan.[41]
Soviet-Afghan war led to increased production in the Pakistani-Afghani border regions, as U.S.-backed mujaheddin militants raised money for arms from selling opium, contributing heavily to the modern Golden Crescent creation. By 1980, 60% of heroin sold in the U.S. originated in Afghanistan.[41] It increased international production of heroin at lower prices in the 1980s. The trade shifted away from Sicily in the late 1970s as various criminal organizations violently fought with each other over the trade. The fighting also led to a stepped up government law enforcement presence in Sicily.
Traffic is heavy worldwide, with the biggest producer being Afghanistan.[42] According to U.N. sponsored survey,[43] as of 2004[update], Afghanistan accounted for production of 87 percent of the world's heroin.[44] Afghan opium kills 100,000 people every year worldwide.[45]
The cultivation of opium in Afghanistan reached its peak in 1999, when 350 square miles (910 km2) of poppies were sown. The following year the Taliban banned poppy cultivation, a move which cut production by 94 percent. By 2001 only 30 square miles (78 km2) of land were in use for growing opium poppies. A year later, after American and British troops had removed the Taliban and installed the interim government, the land under cultivation leapt back to 285 square miles (740 km2), with Afghanistan supplanting Burma to become the world's largest opium producer once more.[46] Opium production in that country has increased rapidly since, reaching an all-time high in 2006. War in Afghanistan once again appeared as a facilitator of the trade.[47] Some 3.3 million Afghans are involved in producing opium.[48]
At present, opium poppies are mostly grown in Afghanistan, and in Southeast Asia, especially in the region known as the Golden Triangle straddling Myanmar, Thailand, Vietnam, Laos and Yunnan province in the People's Republic of China. There is also cultivation of opium poppies in the Sinaloa region of Mexico and in Colombia. The majority of the heroin consumed in the United States comes from Mexico and Colombia. Up until 2004, Pakistan was considered one of the biggest opium-growing countries.
Conviction for trafficking in heroin carries the death penalty in most Southeast Asian, some East Asian and Middle Eastern countries (see Use of death penalty worldwide for details), among which Malaysia, Singapore and Thailand are the most strict. The penalty applies even to citizens of countries where the penalty is not in place, sometimes causing controversy when foreign visitors are arrested for trafficking, for example the arrest of nine Australians in Bali, the death sentence given to Nola Blake in Thailand in 1987, or the hanging of an Australian citizen Van Tuong Nguyen in Singapore.
Many countries and local governments have begun funding programs that supply sterile needles to people who inject illegal drugs in an attempt to reduce these contingent risks and especially the contraction and spread of blood-borne diseases. The Drug Policy Alliance reports that up to 75% of new AIDS cases among women and children are directly or indirectly a consequence of drug use by injection. The United States federal government does not operate needle exchanges, although some state and local governments do support needle exchange programs.
Anthropologists Philippe Bourgois and Jeff Schonberg, who did a decade of field work among homeless heroin and crack addicts in San Francisco, reported that the African-American addicts they observed were more inclined to "direct deposit" heroin into a vein, rather than "skin-popping" their injections. (Skin-popping was a far more widespread practice among the white addicts: "By the midpoint of our fieldwork, most of the whites had given up searching for operable veins and skin-popped. They sank their needles perfunctorily, often through their clothing, into their fatty tissue.") Bourgois and Schonberg describes how the cultural difference between the African-Americans and the whites leads to this contrasting behavior, and also points out that the two different ways to inject heroin comes with different health risks. Skin-popping more often results in abscesses, and direct injection more often leads to fatal overdose and also to hepatitis C and HIV infection.[50]
A heroin overdose is usually treated with an opioid antagonist, such as naloxone (Narcan), or naltrexone, which has high affinity for opioid receptors but does not activate them. This reverses the effects of heroin and other opioid agonists and causes an immediate return of consciousness but may precipitate withdrawal symptoms. The half-life of naloxone is much shorter than that of most opioid agonists, so that antagonist typically has to be administered multiple times until the opioid has been metabolized by the body.
Depending on drug interactions and numerous other factors, death from overdose can take anywhere from several minutes to several hours due to anoxia because the breathing reflex is suppressed by µ-opioids. An overdose is immediately reversible with an opioid antagonist injection. Heroin overdoses can occur due to an unexpected increase in the dose or purity or due to diminished opioid tolerance. However, many fatalities reported as overdoses are probably caused by interactions with other depressant drugs like alcohol or benzodiazepines.[51] It should also be noted that since heroin can cause nausea and vomiting, a significant number of deaths attributed to heroin overdose are caused by aspiration of vomit by an unconscious victim. Some sources quote the median lethal dose (for an average 75 kg opiate-naive individual) as being between 75 and 375 mg.[52] Street heroin is of widely varying and unpredictable purity. This means that the user may prepare what they consider to be a moderate dose while actually taking far more than intended. Also, tolerance typically decreases after a period of abstinence. If this occurs and the user takes a dose comparable to their previous use, the user may experience drug effects that are much greater than expected, potentially resulting in a dangerous overdose.
It has been speculated that an unknown portion of heroin related deaths are the result of an overdose or allergic reaction to quinine, which may sometimes be used as a cutting agent.[53]
A final factor contributing to overdoses is place conditioning. Heroin use is a highly ritualized behavior. While the mechanism has yet to be clearly elucidated, longtime heroin users display increased tolerance to the drug in locations where they have repeatedly administered heroin. When the user injects in a different location, this environment-conditioned tolerance does not occur, resulting in a greater drug effect. The user's typical dose of the drug, in the face of decreased tolerance, becomes far too high and can be toxic, leading to overdose.[54]
A small percentage of heroin smokers and occasionally IV users may develop symptoms of toxic leukoencephalopathy. The cause has yet to be identified, but one speculation is that the disorder is caused by an uncommon adulterant that is only active when heated.[55][56][57] Symptoms include slurred speech and difficulty walking.
Cocaine is sometimes used in combination with heroin, and is referred to as a speedball when injected or moonrocks when smoked together. Cocaine acts as a stimulant, whereas heroin acts as a depressant. Coadministration provides an intense rush of euphoria with a high that combines both effects of the drugs, while excluding the negative effects, such as anxiety and sedation. The effects of cocaine wear off far more quickly than heroin, thus if an overdose of heroin was used to compensate for cocaine, the end result is fatal respiratory depression.
Harm reduction is a public health philosophy that seeks to reduce the harms associated with the use of heroin. One aspect of harm reduction initiatives focuses on the behaviour of individual users. This includes promoting safer means of taking the drug, such as smoking, nasal use, oral or rectal insertion. This attempts to avoid the higher risks of overdose, infections and blood-borne viruses associated with injecting the drug. Other measures include using a small amount of the drug first to gauge the strength, and minimize the risks of overdose. For the same reason, poly drug use (the use of two or more drugs at the same time) is discouraged. Users are also encouraged to not use heroin on their own, as others can assist in the event of an overdose. Injecting heroin users are encouraged to use new needles, syringes, spoons/steri-cups and filters every time they inject and not share these with other users.
Governments that support a harm reduction approach usually fund Needle & Syringe exchange programs, which supply new needles and syringes on a confidential basis, as well as education on proper filtering prior to injection, safer injection techniques, safe disposal of used injecting gear and other equipment used when preparing heroin for injection may also be supplied including citric acid sachets/vitamin C sachets, steri-cups, filters, alcohol pre-injection swabs, sterile water ampules and tourniquets (to stop use of shoe laces or belts).
Another harm reduction measure employed for example in Europe, Canada and Australia are safe injection sites where users can inject heroin and cocaine under the supervision of medically trained staff. Safe injection sites are low threshold and allow social services to approach problem users that would otherwise be hard to reach.[58]
The withdrawal syndrome from heroin (the so-called cold turkey) may begin within 6 to 24 hours of discontinuation of the drug; however, this time frame can fluctuate with the degree of tolerance as well as the amount of the last consumed dose. Symptoms may include: sweating, malaise, anxiety, depression, priapism, extra sensitivity of the genitals in females, general feeling of heaviness, cramp-like pains in the limbs, excessive yawning or sneezing, tears, rhinorrhea, sleep difficulties (insomnia), cold sweats, chills, severe muscle and bone aches; nausea and vomiting, diarrhea, cramps, and fever.[59]
The UK Department of Health's Rolleston Committee report in 1926 established the British approach to heroin prescription to users, which was maintained for the next 40 years: dealers were prosecuted, but doctors could prescribe heroin to users when withdrawing from it would cause harm or severe distress to the patient. This "policing and prescribing" policy effectively controlled the perceived heroin problem in the UK until 1959 when the number of heroin addicts doubled every 16th month during a period of ten years, 1959–1968.[60] The failure changed the attitudes; in 1964 only specialized clinics and selected approved doctors were allowed to prescribe heroin to users. The law was made more restrictive in 1968. Beginning in the 1970s, the emphasis shifted to abstinence and the use of methadone, until now only a small number of users in the UK are prescribed heroin.[61]
In 1994 Switzerland began a trial heroin maintenance program for users that had failed multiple withdrawal programs. The aim of this program is to maintain the health of the user to avoid medical problems stemming from use of illicit street heroin. Reducing drug-related crime and preventing overdoses were two other goals. The first trial in 1994 involved 340 users, although enrollment was later expanded to 1000 based on the apparent success of the program. Participants are allowed to inject heroin in specially designed pharmacies for 15 Swiss francs per day.[62] A national referendum in November 2008 showed 68% of voters supported the plan,[63] introducing heroin prescription into federal law. The trials before were based on time-limited executive ordinances.
The success of the Swiss trials led German, Dutch,[64] and Canadian[65] cities to try out their own heroin prescription programs.[66] Some Australian cities (such as Sydney) have instituted legal heroin supervised injecting centers, in line with other wider harm minimization programs.
Since January 2009 Denmark has prescribed heroin to a few addicts that have tried methadone and subutex without success.[67] Beginning in February 2010, addicts in Copenhagen and Odense will be eligible to receive free heroin. Later in 2010 other cities including Århus and Esbjerg will join the scheme. In total, around 230 addicts will be able to receive free heroin.[68] However, Danish addicts will only be able to inject heroin according to the policy set by Danish National Board of Health.[69] Of the estimated 1500 drug users who do not benefit from the current oral substitution treatment, approximately 900 will not be in the target group for treatment with injectable heroin, either because of "massive multiple drug abuse of non-opioids" or "not wanting treatment with injectable heroin".[70]
In July 2009, the German Bundestag passed a law allowing heroin prescription as a standard treatment for addicts; while heroin prescription was started in 2002, it was only authorized as a large-scale trial.[71]
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