Heroin

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Heroin
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	5462328
Chemical data
Formula	C21H23NO5
Mol. mass	369.41
Pharmacokinetic data
Bioavailability	<35% (oral), 44–61% (inhaled)[1]
Protein binding	0% (morphine metabolite 35%)
Metabolism	hepatic
Half life	3–5 min (IV, inhaled)[2]
Excretion	90% renal as glucuronides, rest biliary
Therapeutic considerations
Pregnancy cat.	Category X
Legal status	Prohibited (S9)(AU) Schedule I(CA) Class A(UK) Schedule I(US)
Dependence Liability	Extremely High
Routes	Inhalation, Transmucosal, Intravenous, Oral, Intranasal, Rectal, Intramuscular

Heroin (INN: diacetylmorphine, BAN: diamorphine) is a semi-synthetic opioid synthesized from morphine, a derivative of the opium poppy. It is the 3,6-diacetyl ester of morphine (hence diacetylmorphine). The white crystalline form is commonly the hydrochloride salt diacetylmorphine hydrochloride.

As with other opiates, heroin is used both as a pain-killer and a recreational drug.

One of the most common methods of heroin use is via intravenous injection (typically known as "shooting up"). If taken orally, heroin undergoes extensive first-pass metabolism via deacetylation, making it a prodrug for the systemic delivery of morphine.^[1] 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.^[2] Once in the brain, it is deacetylated into 3- and 6-monoacetylmorphine and morphine, which bind to μ-opioid receptors resulting in intense euphoria, decreased pain perception, and anxiolytic effects (relief of anxiety).

Frequent administration has a high potential for causing addiction and may quickly lead to tolerance. If a sustained use of heroin for as little as three days is stopped abruptly, withdrawal symptoms can appear. This is much shorter than the withdrawal effects experienced from other common painkillers such as oxycodone and hydrocodone.^[3][4]

Internationally, heroin is controlled under Schedules I and IV of the Single Convention on Narcotic Drugs.^[5] It is illegal to manufacture, possess, or sell heroin in Belgium, Denmark, Germany, the Netherlands, the United States and the UK. However, under the name diamorphine, heroin is a legal prescription drug in the United Kingdom, and in the Netherlands, heroin is available for prescription as the generic drug diacetylmorfine to long-term Heroin addicts. Popular street names for heroin include black tar, smack, junk, skag, horse, brain, chaw, chiva, china white, dust and others. These are specific references to heroin and not used to describe any other drug. Dope could be used to refer to heroin, but may also indicate other drugs, from laudanum a century ago to nearly any contemporary recreational drug.

Contents 1 History 2 Usage and effects 3 Regulation 4 Production and trafficking: The Golden Triangle 4.1 Manufacturing 4.2 History of heroin traffic 4.3 Trafficking 5 Risks of non-medical use 6 Harm reduction approaches to heroin 7 Withdrawal 8 Heroin prescription 9 Drug interactions 10 Popular Culture 10.1 Film & television 10.2 Literature 10.3 Music 11 See also 12 References 13 Literature 14 External links

[edit] History

The opium poppy was cultivated in lower Mesopotamia as long ago as 3400 BC.^[6] The chemical analysis of opium in the 19th century revealed that most of its activity could be ascribed to two ingredients, codeine and morphine.

Heroin was first synthesized in 1874 by C.R. Alder Wright, an English chemist working at St. Mary's Hospital Medical School in London, England. He had been experimenting with combining morphine with various acids. He boiled anhydrous morphine alkaloid with acetic anhydride over a stove 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, who reported the following to 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° (rectal failure).^[7]

Wright's invention, however, did not lead to any further developments, and heroin only became popular after it was independently re-synthesized 23 years later by another chemist, Felix Hoffmann. Hoffmann, working at 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, similar to morphine pharmacologically but less potent and less addictive. But instead of producing codeine, the experiment produced an acetylated form of morphine that was actually 1.5-2 times more potent than morphine itself. Bayer would name the substance "heroin", probably from the word heroisch, German for heroic, because in field studies people using the medicine felt "heroic".^[8]

From 1898 through to 1910 heroin was marketed as a non-addictive morphine substitute and cough suppressant. Bayer marketed heroin as a cure for morphine addiction before it was discovered that heroin is rapidly metabolized into morphine, and as such, "heroin" was basically only a quicker acting form of morphine. The company was somewhat embarrassed by this new finding and it became a historical blunder for Bayer.^[9]

As with aspirin, Bayer lost some of its trademark rights to heroin following the German defeat in World War I.^[10]

In the United States the Harrison Narcotics Tax Act was passed in 1914 to control the sale and distribution of heroin and other opiates. The law did allow heroin to be prescribed and sold for medical purposes. In particular, recreational users could often still be legally supplied with heroin and use it. In 1924, the United States Congress passed additional legislation banning the sale, importation or manufacture of heroin in the United States. It is now a Schedule I substance, and is thus illegal in the United States.

[edit] Usage and effects

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Indicated for: Relief of Extreme Pain Recreational uses: Euphoria Relaxation Other uses: Pain relief Cough suppressant anti-diarrheal

Contraindications: Alcohol Barbiturates and Benzodiazepines Stimulants Other opioids (depends heavily on tolerance)

Side effects[citation needed] Severe:[3] Respiratory arrest, coma, death Central nervous system: Drowsiness Disorientation Delirium Cardiovascular & Respiratory: Lowered heart rate Weak pulse Hypotension Hypoventilation Shallow breathing Respiratory depression Eyes, Ears, nose, and mouth: Dry mouth Pupil constriction ("pinpoint pupils") Miosis Gastrointestinal: Nausea Vomiting (protracted) Constipation Dyspepsia Urinary System: Urinary retention Musculoskeletal: Analgesia Ataxia Muscle spasticity Neurological: Analgesia Physical dependence Psychological: Anxiolysis Confusion Euphoria Psychological dependence Somnolence Skin: Itching Flushing/Rash Diamorphine ampoules for medicinal use

Heroin is used as a recreational drug for the intense euphoria it produces, an effect that diminishes with increased tolerance. Its popularity with recreational drug users, compared to morphine, reportedly stems from its perceived different effects.^[12] However, this perception is not supported by the results of clinical research studies. In controlled studies comparing the physiological and subjective effects of injected heroin and morphine in individuals formerly addicted to opiates, subjects showed no preference for either drug. Equipotent, injected doses had comparable action courses, with no difference in their ability to induce euphoria, ambition, nervousness, relaxation, drowsiness, or sleepiness.^[13] Data acquired from short-term addiction studies did not indicate that heroin tolerance develops more rapidly than tolerance to morphine. The findings have been discussed in relation to the physicochemical properties of heroin and morphine and the metabolism of heroin. When compared to other opioids — hydromorphone, fentanyl, oxycodone, and (pethidine/meperidine), former addicts showed a strong preference for heroin and morphine, suggesting that heroin and morphine are particularly susceptible to abuse and addiction. Morphine and heroin were also much more likely to produce euphoria, and other subjective effects when compared to most opioid analgesics.^[14][15] Heroin can be administered several ways, including snorting and injection, and may be smoked by inhaling its vapors when heated, i.e. "chasing the dragon."

Some users mix heroin with cocaine in a "speedball" or "snowball" combination that usually is injected intravenously, smoked, or snorted, producing a more intense rush than heroin alone, but is more dangerous because the combination of the short-acting stimulant with the longer-acting depressant increases the risk of seizure, or overdose with one or both drugs.

Once in the brain, heroin is rapidly metabolized to 6-acetylmorphine and morphine by removal of the acetyl groups and thus serves as a prodrug. Morphine is unable to cross the blood-brain barrier as quickly as heroin, which gives heroin a comparably shorther onset of action. In either case, a morphine binds to opioid receptors, inducing the opioid high.

The onset of heroin's effects depends upon the route of administration. Orally, heroin is completely metabolized in vivo to morphine before crossing the blood-brain barrier; the effects are the same as with oral morphine. Snorting results in an onset within 3 to 5 minutes; smoking results in an almost immediate effect that builds in intensity; intravenous injection induces a rush and euphoria usually taking effect within 30 seconds; intramuscular and subcutaneous injection take effect within 3 to 5 minutes.

Heroin is metabolized into morphine, a μ-opioid receptor agonist. It acts on endogenous μ-opioid receptors that are present throughout the brain, spinal cord and gut in all mammals. The μ-opioid receptor also binds endogenous opioid peptides such as β-endorphin, Leu-enkephalin, and Met-enkephalin. Repeated use of heroin results in a number of physiological changes, including decreases in the number of μ-opioid receptors. These physiological alterations lead to tolerance and dependance, and the cessation of heroin use results in extremely uncomfortable symptoms including pain, anxiety, muscle spasms, and insomnia. This set of symptoms is called the opiate withdrawal syndrome. It has an onset 6 to 8 hours after the last dose of heroin. Morphine also binds to δ- and κ-opioid receptors. There has also been some controversy regarding whether heroin binds to a subtype of μ-opioid receptors that is not targeted by morphine but is activated by the morphine metabolite morphine-6β-glucuronide.^[16]

The heroin dose used for recreational purposes depends strongly on the frequency of use. A first-time user typically ingests between 5 and 20 mg of heroin, but an individual who is heavily dependent on the drug may require several hundred mg per day.^[17]

Large doses of heroin can be fatal. 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). It can sometimes be difficult to determine whether a heroin death was an accident, suicide or murder as with the deaths of Sid Vicious, Joseph Krecker, Janis Joplin, Tim Buckley, Jim Morrison^{[citation needed]}, Layne Staley, and Bradley Nowell which have been attributed to heroin overdose.^[18]

[edit] Regulation

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, to 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 it 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.

[edit] Production and trafficking: The Golden Triangle

[edit] Manufacturing

Heroin is produced for the black market by refining opium. The first step of this process involves isolation of morphine from opium. This crude morphine is then acetylated by heating with acetic anhydride. Purification of the obtained crude heroin and conversion to the the hydrochloride salt results in a water-soluble form of the drug that is a white or yellowish powder.

Crude opium is carefully dissolved in hot water but the resulting hot soup is not boiled. Mechanical impurities - twigs - are scooped together with the foam. The mixture is then made alkaline by gradual addition of lime. Lime causes a number of unwelcome components present in opium to precipitate out of the solution. (The impurities include inactive alkaloids, resins, proteins). The precipitate is removed by filtration through a cloth, washed with additional water and discarded. The filtrates containing the water-soluble calcium salt of morphine (calcium morphinate) are then acidified by careful addition of ammonium chloride. This causes freebase morphine to precipitate. The morphine precipitate is collected by filtration and dried before the next step. The crude morphine (which makes only about 10% of the weight of opium) is then heated together with acetic anhydride at 85 °C (185 °F) for six hours. The reaction mixture is then cooled, diluted with water, made alkaline with sodium carbonate, and the precipitated crude heroin is filtered and washed with water. This crude water-insoluble freebase product (which by itself is usable, for smoking) is further purified and decolourised by dissolution in hot alcohol, filtration with activated charcoal and concentration of the filtrates. The concentrated solution is then acidified with hydrochloric acid, diluted with ether, and the precipitated heroin hydrochloride is collected by filtration. This precipitate is the so-called "no. 4 heroin", commonly known as "china white". Heroin freebase cut with a small amount of caffeine (to help vaporise it more efficiently), typically brown in appearance, is known as called "no. 3 heroin". These two forms of heroin are the standard products exported to the Western market. Heroin no. 3 predominates on the European market, where heroin no. 4 is relatively uncommon. Another form of heroin is "black tar" which is common in the western United States and is produced in Mexico.

The initial stage of opium refining - the isolation of morphine - is relatively easy to perform in rudimentary settings - even by substituting suitable fertilizers for pure chemical reagents. However, the later steps (acetylation, purification, and conversion to the hydrochloride salt) are more involved - they use large quantities of chemicals and solvents and they require both skill and patience. The final step is particularly tricky as the highly flammable ether can easily ignite during positive-pressure filtration (the explosion of vapor-air mixture can obliterate the refinery). If the ether does ignite, the result is a catastrophic explosion.

[edit] History of heroin traffic

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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.

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 the second world war, 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 from Iran^{[citation needed]} westward into Europe and the United States. 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 abuse led most western countries to declare heroin a controlled substance by the latter half of the 20th century.

Between the end of World War II and the 1970s, much of the opium consumed in the west was grown in Iran^{[citation needed]}, but in the late 1960s, under pressure from the U.S. and the United Nations, Iran^{[citation needed]} engaged in anti-opium policies. While opium production never completely ended in Iran^{[citation needed]}, the decline in production in those countries led to the development of a major new cultivation base in the so-called "Golden Triangle" region in South East Asia. In 1970-71, high-grade heroin laboratories opened in the Golden Triangle. This changed the dynamics of the heroin trade by expanding and decentralizing the trade. Opium production also increased in Afghanistan due to the efforts of Turkey and Iran^{[citation needed]} to reduce production in their respective countries. Lebanon, a traditional opium supplier, also increased its role in the trade during years of civil war.^{[citation needed]}

Soviet-Afghan war led to increased production in the Pakistani-Afghani border regions. 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. All of this combined to greatly diminish the role of the country in the international heroin trade.^{[citation needed]}

[edit] Trafficking

See also: Opium production

Traffic is heavy worldwide, with the biggest producer being Afghanistan.^[19] According to U.N. sponsored survey,^[20] as of 2004, Afghanistan accounted for production of 87 percent of the world's heroin.^[21] Opium production in that country has increased rapidly since, reaching an all-time high in 2006. War once again appeared as a facilitator of the trade.^[22]

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. However, the efforts of Pakistan's Anti-Narcotics Force have since reduced the opium growing area by 59% as of 2001^{[citation needed]}.

Conviction for trafficking in heroin carries the death penalty in most South-east Asia and some East Asia 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 or the hanging of an Australian citizen Van Tuong Nguyen in Singapore, both in 2005.

Sandra Gregory has written an autobiography covering her experience of getting caught with Heroin at a Thai airport.

[edit] Risks of non-medical use

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• For intravenous users of heroin (and any other substance), the use of non-sterile needles and syringes and other related equipment leads to several serious risks:
  • the risk of contracting blood-borne pathogens such as HIV and hepatitis
  • the risk of contracting bacterial or fungal endocarditis and possibly venous sclerosis
  • abscesses
• Poisoning from contaminants added to "cut" or dilute heroin
• Chronic constipation
• Addiction and increasing tolerance
• Physical dependence can result from prolonged use of all opioids, resulting in withdrawal symptoms on cessation of use
• Decreased kidney function (although it is not currently known if this is due to adulterants used in the cut)^[23]

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. But despite the immediate public health benefit of needle exchanges, some see such programs as tacit acceptance of illicit drug use. The United States federal government does not operate needle exchanges, although some state and local governments do support needle exchange programs.

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 and the beginning of withdrawal symptoms when administered intravenously. 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 opiate 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 opiate tolerance. However, many fatalities reported as overdoses are probably caused by interactions with other depressant drugs like alcohol or benzodiazepines.^[24] 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 vomitus by an unconscious victim.

The LD₅₀ for a physically addicted person is prohibitively high,^{[citation needed]} to the point that there is no general medical consensus on where to place it. In fact, there is no upper limit to the amount of tolerance that can occur in a heavy user. Several studies done in the 1920s gave users doses of 1,600–1,800 mg of heroin, and no adverse effects were reported. Even for a non-user, the LD₅₀ can be placed above 350 mg^{[citation needed]} though some sources give a figure of between 75 and 375 mg for a 75 kg person.^[25]

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.^[26]

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.^[27]

A small percentage of heroin smokers and 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.^[28][29][30] Symptoms include slurred speech and difficulty walking.

[edit] Harm reduction approaches to heroin

Proponents of the harm reduction philosophy seek to minimize the harms that arise from the recreational use of heroin. Safer means of taking the drug, such as smoking or nasal, oral and rectal insertion, are encouraged, due to injection having higher risks of overdose, infections and blood-borne viruses. Where the strength of the drug is unknown, users are encouraged to try a small amount first to gauge the strength, to 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. Heroin users who choose to inject should always 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 often run 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).

[edit] Withdrawal

The withdrawal syndrome from heroin 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, yawning, tears, sleep difficulties (insomnia), cold sweats, chills, severe muscle and bone aches; nausea and vomiting, diarrhea, cramps, and fever.^[31] Many users also complain of a painful condition, the so-called "itchy blood", which often results in compulsive scratching that causes bruises and sometimes ruptures the skin, leaving scabs. Abrupt termination of heroin use often causes muscle spasms in the legs (restless leg syndrome); hence "kicking" has been used as a slang term for heroin withdrawal. Discontinuation of heroin can also cause goose bumps, and this symptom is the basis for the expression "going cold turkey". The intensity of the withdrawal syndrome is variable depending on the dosage of the drug used and the frequency of use. Very severe withdrawal can be precipitated by administering an opioid antagonist to a heroin addict.

Three general approaches are available to ease the physical part of opioid withdrawal. The first is to substitute a longer-acting opioid such as methadone or buprenorphine for heroin or another short-acting opioid and then slowly taper the dose.

In the second approach, benzodiazepines such as diazepam (Valium) may temporarily ease the anxiety, muscle spasms, and insomnia associated with opioid withdrawal. The most common benzodiazepine employed is oxazepam (Serax). The use of benzodiazepines must be carefully monitored because these drugs have abuse potential, and many opioid users also use other central nervous system depressants, especially alcohol. Also, although extremely unpleasant, opioid withdrawal is seldom fatal, whereas complications related to withdrawal from benzodiazepines, barbiturates and alcohol (such as epileptic seizures, cardiac arrest, and delirium tremens) can prove hazardous and are potentially life-threatening.

Many symptoms of opioid withdrawal are due to rebound hyperactivity of the sympathetic nervous system, which can be suppressed with clonidine (Catapres), a centrally-acting alpha-2 agonist primarily used to treat hypertension. Another drug sometimes used to relieve the "restless legs" symptom of withdrawal is baclofen, a muscle relaxant. Diarrhea can likewise be treated with the peripherally active opioid drug loperamide.

Methadone is another μ-opioid agonist most often used to substitute for heroin in treatment for heroin addiction. Compared to heroin, methadone is well (but slowly) absorbed by the gastrointestinal tract and has a much longer duration of action of approximately 24 hours. Thus methadone maintenance avoids the rapid cycling between intoxication and withdrawal associated with heroin addiction. In this way, methadone has shown success as a substitute for heroin; despite bearing about the same addiction potential as heroin, it is recommended for those who have repeatedly failed to complete withdrawal or have recently relapsed. Patients properly stabilized on methadone display few subjective effects to the drug (i.e., it does not make them "high"), and are unable to obtain a "high" from other opioids except with very high doses. Methadone, since it is longer-acting, produces withdrawal symptoms that appear later than with heroin, but usually last considerably longer and can in some cases be more intense. Methadone withdrawal symptoms can potentially persist for over a month, compared to heroin where significant physical symptoms subside within 4 days.

Buprenorphine is another opiate that was recently licensed for opioid substitution treatment. As a μ-opioid receptor partial agonist, patients develop a less tolerance to it than to heroin or methadone due to a "ceiling effect." Patients are unable to obtain a "high" from other opioids during buprenorphine treatment except with very high doses. It also has less severe withdrawal symptoms than heroin when discontinued abruptly, although the duration of the withdrawal syndrome is often longer than that seen with heroin. It is usually administered sublingually (dissolved under the tongue) every 24-48 hrs. Buprenorphine is also a κ opioid receptor antagonist, which led to speculation that the drug might have additional antidepressant effects; however, no significant difference was found in symptoms of depression between patients receiving buprenorphine and those receiving methadone.^[32]

Researchers at Johns Hopkins University have been testing a sustained-release "depot" form of buprenorphine that can relieve cravings and withdrawal symptoms for up to six weeks.^[33] A sustained-release formulation would allow for easier administration and adherence to treatment, and reduce the risk of diversion or misuse.

Three opioid antagonists are available: naloxone and the longer-acting naltrexone and nalmefene. These medications block the ability of heroin, as well as the other opioids to bind to the receptor site. Recent studies have suggested that the addition of naltrexone may improve the success rate in treatment programs when combined with the traditional therapy.^{[citation needed]}

Scientists at the University of Chicago undertook preliminary development of a heroin vaccine in monkeys during the 1970s, but it was abandoned. There were two main reasons for this. Firstly, when immunized monkeys had an increase in dose of x16, their antibodies became saturated and the monkey had the same effect from heroin as non-immunized monkeys. Secondly, until they reached the x16 point immunized monkeys would substitute other drugs to get a heroin-like effect. These factors suggested that immunized human users would simply either take massive quantities of heroin, or switch to other drugs.

There is also a controversial treatment for heroin addiction based on an Iboga-derived African drug, ibogaine. Many people travel abroad for ibogaine treatments that generally interrupt substance use disorders for 3-6 months or more in up to 80% of patients.^[34] Relapse may occur when the person returns home to their normal environment however, where drug seeking behavior may return in response to social and environmental cues.^{[citation needed]} Ibogaine treatments are carried out in several countries including Mexico and Canada as well as, in South and Central America and Europe. Opioid withdrawal therapy is the most common use of ibogaine. Some patients find ibogaine therapy more effective when it is given several times over the course of a few months or years. A synthetic derivative of ibogaine, 18-methoxycoronaridine was specifically designed to overcome cardiac and neurotoxic effects seen in some ibogaine research but, the drug has not yet found its way into clinical research..

[edit] Heroin prescription

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 forty 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 heroinists doubled every sixteenth month during a period of ten years, 1959-1968. ^[35]. 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. Begining 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.^[36]

In 1994 Switzerland began a trial heroin maintence program for users that had failed multiple withdrawal programs. The aim of this program is to maintain the health of the user in order to avoid medical problems stemming from the 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 dose.^[37]

The success of the Swiss trials led German, Dutch,^[38] and Canadian^[39] cities to try out their own heroin prescription programs.^[40] Some Australian cities (such as Sydney) have instituted legal heroin supervised injecting centers, in line with other wider harm minimization programs. Although heroin is decriminalized inside the injection room, the drug is not available by prescription, and remains illegal outside the injecting room.^{[citation needed]}

[edit] Drug interactions

Opioids are strong central nervous system depressants, but regular users develop physiological tolerance. In combination with other central nervous system depressants, heroin may still kill even experienced users, particularly if their tolerance to the drug has reduced or the strength of their usual dose has increased.

Toxicology studies of heroin-related deaths reveal frequent involvement of other central nervous system depressants, including alcohol, benzodiazepines such as temazepam (Restoril; Normison), and, to a rising degree, methadone. Ironically, benzodiazepines are often used in the treatment of heroin addiction while they cause much more severe withdrawal symptoms.

Cocaine sometimes proves to be fatal when used in combination with heroin. Though "speedballs" (when injected) or "moonrocks" (when smoked) are a popular mix of the two drugs among users, combinations of stimulants and depressants can have unpredictable and sometimes fatal results. In the United States in early 2006, a rash of deaths was attributed to either a combination of fentanyl and heroin, or pure fentanyl masquerading as heroin particularly in the Detroit Metro Area; one news report refers to the combination as 'laced heroin', though this is likely a generic rather than a specific term.^[41]

[edit] Popular Culture

[edit] Film & television

The 1996 Danny Boyle film Trainspotting, based on the book by Irvine Welsh, depicts heroin users in the areas around Edinburgh in Scotland. Other movies that deal with heroin users include Quentin Tarantino's Pulp Fiction in which Vincent Vega played by John Travolta struggles with heroin addiction, the 1955 Frank Sinatra film The Man with the Golden Arm; the 1969 film More; the 1971 Al Pacino film The Panic in Needle Park; the 1981 true story Christiane F. - Wir Kinder vom Bahnhof Zoo; The Basketball Diaries, based on the diary of author, poet, and musician Jim Carroll during his heroin addiction; the 1997 film Gridlock'd starring Tupac Shakur and Tim Roth as heroin users struggling to get into rehab; the 1998 television movie Gia about drug-addicted supermodel Gia Carangi; and the 2000 film Requiem for a Dream. Throughout the third season of Fox's 24, the show's protagonist, Jack Bauer, struggles with using heroin. In American Gangster (2007), Denzel Washington portrays the 1970s drug kingpin, Frank Lucas, who smuggled heroin on military transport flights from Vietnam for eventual distribution on the East Coast. Candy is a 2006 Australian film starring Heath Ledger that depicts the life of a heroin addict. Also, in the Broadway musical Rent and the movie adaptation of Rent, two of the main characters, Mimi and Roger, were both once heroin addicts, Roger having come off a year of withdrawal the year prior to when the musical/movie takes place, and Mimi struggling to quit throughout the course of the story.

Little Fish is a 2005 Australian film directed by Rowan Woods and stars Cate Blanchett and Hugo Weaving. The film focusses on the devastating effects of heroin addiction throughout the stages of addiction and the struggle to come clean upon both the user and those affected around them.

The 1989 miniseries Traffik is set in three countries (the UK, Germany, and Pakistan) and follows the lives of people in each country who all play different roles in the trafficking of heroin, from the UK politician who is trying to stem the flow of heroin into the UK (but whose daughter is addicted), the businessman and his wife who run a trafficking business in Germany, the Pakistan businessman who controls the shipping out of his country, and the farmers who grow the opium crops.

In 2000 the miniseries was adapted into the American film Traffic with the setting shifted to America and Mexico and the focus moved from heroin to the cocaine trade.

The Australian drama serial A Country Practice had a major heroin storyline during 1988. It involved the character of Sophie Elliott (portrayed by Katrina Sedgewick) having a heroin addiction. She eventually developed AIDS and she died. These episodes drew huge ratings and were widely praised by Australian medical authorities for the way they tackled the subject.

In 2004, the TV show LOST featured a character who is a heroin addict named Charlie Pace. Charlie was a member of a fictional band named Drive Shaft before crashing on the island and it is revealed that he became addicted during his band's success. Charlie's addiction to heroin is a minor but prominent subplot throughout the first and second season of the series.

[edit] Literature

Before the film Trainspotting, there was Irvine Welsh's novel of the same name. A 2007 book entitled The Heroin Diaries by author and musician Nikki Sixx from Motley Crue and Sixx:A.M. chronicles his heroin addiction in his diary between the years 1986-1987, as well as his chronic extreme hedonism, attitudes, drug use and his inevitable route to dying and coming back to life. Author William S. Burroughs also wrote about his experiences with heroin in numerous books, starting with the 1953 semi-autobiographical Junkie (aka Junky). Even earlier, in 1922, Aleister Crowley wrote Diary of a Drug Fiend. Allen Hoey's 2006 novel, Chasing the Dragon, examines the use of heroin among jazz musicians in the 1950s.

[edit] Music

The well-known jazz artist Miles Davis was a heroin addict from about 1950 to 1954. His album Kind of Blue (recorded in 1959) is supposed to sound like a heroin high feels.^[42] This album is widely regarded as one of the best jazz albums ever.^[43][44]

John Lennon wrote the song "Cold Turkey" in 1969 about his and Yoko Ono's attempts to get off the drug, which the pair started using after she suffered a miscarriage. David Bowie's first single "Space Oddity" was seemingly about his experiences with heroin, as his 1980 single "Ashes to Ashes" included the lines that refer to Major Tom as "...a junkie/strung out on heaven's high/hitting an all-time low".^[45]

The Rolling Stones' 1973 song "Coming Down Again" was written by Keith Richards about his experiences with heroin, as was "Before They Make Me Run". Mick Jagger wrote the song "Monkey Man", and with Marianne Faithfull wrote "Sister Morphine". The band's 1971 album Sticky Fingers featured a drug reference in every track.^[45]

A number of songs by the Velvet Underground refer to heroin, including "I'm Waiting For The Man" and the aptly-named "Heroin". The Stranglers' single "Golden Brown", from the late 1970s, referred to a batch of brown heroin from Afghanistan that arrived in the UK around that time. Another UK band, The Only Ones released a one hit wonder, "Another Girl, Another Planet", in which every single line could be interpreted as a reference to a girl or heroin."^[45]

Dee Dee Ramone(nee Douglas Colvin) of the US punk band The Ramones used the drug and wrote the song "Chinese Rocks", thought the rest of the band initially rejected the song as being too blatantly about drug use. The Heartbreakers performed the first and more famous version of the song. The songs "Mr. Brownstone" and "Bad Obsession" by Guns N' Roses also deal with heroin.

The Red Hot Chili Peppers have numerous drug refences in their music, most famously "Under the Bridge", a song about Anthony Kiedis's experiences in the chicano-run areas of Los Angeles where he used to score. "Knock Me Down" was another Red Hot Chili Peppers song about heroin, this time about the band's first guitarist Hillel Slovak who died after overdosing on a mix of cocaine and heroin. The metal/rock band System of a Down wrote the song "She's Like Heroin". Also, Black Sabbath wrote a song, "Hand of Doom", which talks about the negative effects of heroin.

The A Perfect Circle song "Weak and Powerless" is about heroin addiction, as is The Darkness song "Givin' Up" from their debut album Permission to Land. Nikki Sixx also wrote a song about his heroin addiction, which is included on their 1987 album "Girls, Girls, Girls" titled "Dancing on Glass".^[45]

Ville Valo, frontman of Finnish rock band HIM, wrote "Killing Loneliness" about Brandon Novak's addiction to heroin. In an interview Valo stated that when he asked Novak why he used the drug, Novak replied "It was my way of 'Killing Loneliness'"

The London Suede recorded many songs about heroin, and drug culture in general. They have two different songs, Heroine (from Dog Man Star) and Heroin (b-side to the Attitude single), which refer to lead singer Brett Anderson's addiction to the drug.

The Used song, "Let It Bleed" refers to frontman, Bert McCracken's heroin addiction before the band started. The song starts with "This poison's my intoxication, I broke the needle off in my skin". Another song by The Used that also refer McCracken's past addiction to crystal meth is Say Days Ago from their debut album The Used.

80's pop superstar Boy George was caught up in using heroin which was highly publicized in the media. He also wrote and recorded a song of his experience with the drug titled "You Are My Heroin" in 1988.

Rozz Williams' final album before his suicide, The Whorse's Mouth, dealt with his heroin addiction.^[46] Kill Hannah's song "Lips Like Morphine" (from their album of the same name) refers to the lead singer's want of an addictive woman that will "knock" him out with one touch.

Many songs by singer song writer Elliott Smith such as "A Fond Farewell", and "King' Crossing" refer to his addiction with heroin.

Goldfrapp made the song Ride a White Horse, which many claim refers to Alison Goldfrapp's heroin usage.

Other notable artists who have had experiences with or who wrote about heroin include Sid Vicious, Dave Mustaine, Pete Doherty, Lynyrd Skynyrd, Eric Clapton, Jerry Garcia, Pete Townshend, Ezra Crack, Trent Reznor, Layne Staley, David Reilly, Nikki Sixx, John Frusciante, Steven Tyler, Kurt Cobain, Scott Weiland, Brian Jones, Chet Baker, Tim Buckley, Jesse Ed Davis, Dave Matthews, Brad Nowell, Johnny Thunders, Janis Joplin, Jimmy Page, Charlie Parker, Jim Morrison, Ray Charles, Billie Holiday, Phil Lynott, Frankie Lymon, Mike Bloomfield, Miles Davis, Courtney Love, Mike McCready, Phil Anselmo, B.G., James Brown, Gil Scott-Heron, Amy Winehouse, Jay-Z Raekwon the Chef, and Ghostface Killah.

[edit] See also

• Morphine
• Opioids
• Black Tar Heroin
• Cheese (recreational drug)
• China White
• HIV in Yunnan
• Drugs and prostitution
• Ibogaine
• Monoacetylmorphine
• Dipropanoylmorphine
• Diacetyldihydromorphine
• Recreational drug use
• Psychoactive drug
• The Great Binge
• Opium
• Polish heroin
• Poppy
• Drug injection
• Illegal drug trade
• Illicit drug use in Australia
• Entomotoxicology
• Trainspotting

[edit] References

[edit] Literature

• Diary Of A Drug Fiend by Aleister Crowley (1922)
• Heroin (1998) ISBN 1-56838-153-0
• Heroin Century (2002) ISBN 0-415-27899-6
• This is Heroin (2002) ISBN 1-86074-424-9
• The Heroin User's Handbook by Francis Moraes (paperback 2004) ISBN 1-55950-216-9
• The Little Book of Heroin by Francis Moraes (paperback 2000) ISBN 0-914171-98-4
• Heroin: A True Story of Addiction, Hope and Triumph by Julie O'Toole (paperback 2005) ISBN 1-905379-01-3
• The Heroin Diaries: A Year in the Life of a Shattered Rockstar by Nikki Sixx (2007) ISBN 978-0743486-28-6

[edit] External links

• EMCDDA drugs profiles: heroin (2007)
• Geopium: Geopolitics of Illicit Drugs in Asia, especially opium and heroin production and trafficking in and around Afghanistan and Burma (Articles and maps and French and English)
• Drugs Factfile what you really need to know
• The mismanagement of methadone
• National Alliance of Advocates for Buprenorphine Treatment - non-profit education website for treatment of Heroin addiction
• NIDA InfoFacts on Heroin
• ONDCP Drug Facts
• United States Department of State fact sheet: anti-narcotics efforts in Pakistan - dated June 7, 2002
• BBC Article entitled 'When Heroin Was Legal'. References to the United Kingdom and the United States
• Harm reduction strategies in relation to heroin and other illicit drugs
• Heroin news page - Alcohol and Drugs History Society

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