Heroin

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Heroin
Systematic (IUPAC) name
N/A
Identifiers
CAS number 561-27-3
ATC code  ?
PubChem 9844225
ChemSpider 4575379
Chemical data
Formula C21H24ClNO5
Mol. mass 405.87196
SMILES eMolecules & PubChem
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 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

Contents

[edit] Description

A narcotic analgesic that may be habit-forming. It is a controlled substance (opium derivative) listed in the U.S. Code of Federal Regulations, Title 21 Parts 329.1, 1308.11 (1987). Sale is forbidden in the United States by Federal statute. (Merck Index, 11th ed). Diacetylmorphine (INN), also known as diamorphine (BAN) and heroin, is a semi-synthetic opioid drug 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, however heroin freebase may also appear as a white powder.

As with other opioids, diacetylmorphine is used as both a pain-killer and a recreational drug and has high potential for abuse. Frequent and regular administration is associated with tolerance, moderate physical dependence, and severe psychological dependence which often develops into addiction. Despite this, heroin has been proven to act as an extraordinary fever reducer.

Internationally, diacetylmorphine is controlled under Schedules I and IV of the Single Convention on Narcotic Drugs.<ref>Template:Cite web Referring URL = http://www.incb.org/incb/yellow_list.html</ref> It is illegal to manufacture, possess, or sell diacetylmorphine without a licence 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. In the Netherlands, under the name diacetylmorphine, it is available for prescription to long-term addicts.

[edit] General Properties

*Molecular Weight

405.87196

*Molecular Formula

C21H24ClNO5

*IUPAC NAME

N/A

*Canonical Smiles

CC(=O)OC1C=CC2C3CC4=C5C2(C1OC5=C(C=C4)OC(=O)C)CCN3C.Cl

*Isomeric Smiles

CC(=O)O[C@H]1C=C[C@H]2[C@H]3CC4=C5[C@]2([C@H]1OC5=C(C=C4)OC(=O)C)CCN3C.Cl

*XLogP

N/A

*Topological Polar Surface Area

65.1

[edit] History

Image:BayerHeroin.png
Old advertisement for Bayer Heroin.
Image:Bayer Heroin bottle.jpg
Bayer Heroin bottle.

The opium poppy was cultivated in lower Mesopotamia as long ago as 3400 BC.<ref>Template:Cite web</ref> 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, 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).<ref>Template:Cite web Note: this is an annotated excerpt of Wright, C.R.A. (1874). "On the Action of Organic Acids and their Anhydrides on the Natural Alkaloids". Journal of the Chemical Society 27: 1031–1043. doi:10.1039/js8742701031. </ref>

Wright's invention, however, 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: 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 one and a half to two 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".<ref>Bowden, Mary Ellen. Pharmaceutical Achievers. Philadelphia: Chemical Heritage Foundation, 2002.</ref>

From 1898 through to 1910, under the name heroin, diacetylmorphine 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 it is rapidly metabolized into morphine, and as such, heroin was essentially a quicker acting form of morphine. The company was embarrassed by this new finding and it became a historic blunder for Bayer.<ref>How aspirin turned hero, Sunday Times article, 13 September 1998, reproduced on a BLTC website, accessed 18 March 2009</ref>

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.<ref> 

 Template:Cite web</ref>

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. This law did allow the drug to be prescribed and sold for medical purposes. In 1924, the United States Congress passed additional legislation banning the sale, importation or manufacture. It is now a Schedule I substance, and is thus illegal in the United States.

[edit] Pharmacology

When taken orally, diacetylmorphine undergoes extensive first-pass metabolism via deacetylation, making it a prodrug for the systemic delivery of morphine.<ref name="Sawynok 1986">Sawynok J (January 1986). "The therapeutic use of heroin: a review of the pharmacological literature". Can. J. Physiol. Pharmacol. 64 (1): 1–6. PMID 2420426. </ref> 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.<ref name="Klous 2005">Klous MG, Van den Brink W, Van Ree JM, Beijnen JH (December 2005). "Development of pharmaceutical heroin preparations for medical co-prescription to opioid dependent patients". Drug Alcohol Depend 80 (3): 283–95. doi:10.1016/j.drugalcdep.2005.04.008. PMID 15916865. </ref> Once in the brain, it then is deacetylated into 6-monoacetylmorphine (6-MAM) and 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.<ref>Inturrisi CE, Schultz M, Shin S, Umans JG, Angel L, Simon EJ (1983). "Evidence from opiate binding studies that heroin acts through its metabolites". Life Sci. 33 Suppl 1: 773–6. PMID 6319928. </ref> 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.<ref>Histamine release by morphine and diamorphine in man. & Cutaneous Complications of Intravenous Drug Abuse</ref>

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. Template:Fact These physiological alterations lead to tolerance and dependence, so that cessation of diacetylmorphine use results in a set of extremely uncomfortable symptoms including pain, anxiety, muscle spasms, and insomnia called the opioid withdrawal syndrome. Depending on usage it has an onset 4 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.<ref>Brown GP, Yang K, King MA, et al (July 1997). "3-Methoxynaltrexone, a selective heroin/morphine-6beta-glucuronide antagonist". FEBS Lett. 412 (1): 35–8. doi:10.1016/S0014-5793(97)00710-2. PMID 9257684. </ref> 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®).

[edit] Usage and effects

[edit] Medical use

Under the name diamorphine, diacetylmorphine is prescribed as a strong analgesic in the United Kingdom, where it is given via subcutaneous, intramuscular or intravenous route. Its use includes treatment for acute pain, such as in severe trauma, myocardial infarction, and following surgery, and chronic pain, including in cancer. 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.<ref>http://www.ukhra.org/statements/diamorphine_shortage_uk.html</ref> Due to this, many hospitals changed to using morphine instead of diamorphine. Although there is no longer a problem with its manufacture, many hospitals 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.

[edit] Recreational use

Image:Heroin Stamp.jpg
One stamp of Heroin

Diacetylmorphine is used as a recreational drug for the profound relaxation and intense euphoria it produces, although the latter effect diminishes with increased tolerance. Its popularity with recreational drug users, compared to morphine, reportedly stems from its perceived different effects.<ref>Tschacher W, Haemmig R, Jacobshagen N. (2003). "Time series modeling of heroin and morphine drug action". Psychopharmacology. doi:10.1007/s00213-002-1271-3. PMID 12404073. </ref> 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. Any intravenous opioid will induce rapid, profound effects, but 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 abuse, 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.<ref name="martin and fraser">Martin WR, Fraser HF (September 1961). "A comparative study of physiological and subjective effects of heroin and morphine administered intravenously in postaddicts". J. Pharmacol. Exp. Ther. 133: 388–99. PMID 13767429. </ref> 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.<ref name="martin and fraser" />

One of the most common methods of illicit diacetylmorphine use is via intravenous injection (colloquially termed "shooting up"). Heroin base (commonly found in the UK and 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 its hydrochloride salt, requiring just water to dissolve. Users tend to initially inject in the easily accessible veins in the arm, but as these veins collapse over time through damage caused by the acid, the user will often resort to injecting in other veins such as those in the legs, groin or neck.

Recreational users may also administer the drug through means of 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. 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. The user follows the "blob" of heroin with the intention of inhaling, through the tube, as much of the smoke as possible - i.e. "chasing the dragon."

The onset of diacetylmorphine's effects depends upon the route of administration. Orally, since diacetylmorphine 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.

The diacetylmorphine dose used for recreational purposes depends strongly on the frequency of use. A first-time user typically ingests between 5 and 20 mg of diacetylmorphine, but an individual who is heavily dependent on the drug may require several hundred mg per day.<ref>Notes on heroin dosage & tolerance. Erowid's Vault, 2001.</ref>

Large doses of diacetylmorphine 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 diacetylmorphine death was an accident, suicide or murder. Examples include the overdose deaths of Sid Vicious, Janis Joplin, Tim Buckley, Layne Staley, Bradley Nowell, Jim Morrison, Ted Binion, and River Phoenix.<ref>First murder charge over heroin mix that killed 400 - World - Times Online</ref>

[edit] Effects

Image:Rational scale to assess the harm of drugs (mean physical harm and mean dependence).svg
Data from The Lancet shows diacetylmorphine to be the most dependence causing and most harmful of 20 drugs.<ref name="Nutt">Development of a rational scale to assess the harm of drugs of potential misuse, David Nutt, Leslie A. King, William Saulsbury, Colin Blakemore, The Lancet website, 24 March 2007, accessed 31 January 2009 (free registration required for full access)</ref>
</div> </div> Central nervous system:Cardiovascular & Respiratory:Eyes, Ears, mouth, and nose:thumb|right|190px|Main short-term effects of heroin usage.<ref name=ONDCP>[http://www.whitehousedrugpolicy.gov/drugfact/heroin/heroin_ff.html#healtheffects Office of National Drug Control Policy (ONDCP): Heroin Facts & Figures] Retrieved on 11 February, 2009</ref>Gastrointestinal:Urinary System:thumb|right|200px|Main long-term effects of heroin usage.<ref name=ONDCP/>Musculoskeletal:Neurological:Psychological:Skin:
  • Itching
  • Flushing/Rash
Image:Diamorphine ampoules.JPG
Diamorphine ampoules for medicinal use
Indicated for:
  • Relief of Extreme Pain

Recreational uses:

Other uses:

Contraindications:

[edit] Regulation

Template:Unreferenced section 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.

[edit] Price

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 45-55€ per gram. The price of white heroin is reported only by a few European countries and ranged between 27€ and 110€ per gram.<ref>Template:Cite book</ref>

The United Nations Office on Drugs and Crime claims in its 2008 World Drug Report that typical US retail prices are 172 dollars per gram.<ref>Template:Cite book</ref>

[edit] Production and trafficking: The Golden Triangle

Image:HeroinWorld-en.svg
Primary worldwide producers of heroin.

[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 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 morphine (as a free phenol) 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 decolorised 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 the purest form of heroin collected by filtration. This precipitate is the so-called "no. 4 heroin", commonly known as "china white". China white is heroin in its purest form. Heroin freebase cut with a small amount of caffeine (to help vaporise it more efficiently), typically brown in appearance, is known as "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.

Heroin can be produced in small quantities, often by end users, from morphine which is obtained from pharmaceuticals, or much less often from poppy straw, opium &c. The morphine can also be itself synthesised from codeine. The process involves wetting the morphine-bearing powder with acetic anhydride or chloride and igniting it, covering with foil and baking in an oven at 80°C for one to five hours and similar processes. The result in a mixture of heroin, morphine, 6-monoacetylmorphine and 3-monoacetylmorphine as well as any other drugs present in the precursors and some of their acetylated derivatives such as acetylcodeine.

[edit] History of heroin traffic

Template:Original research

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. 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. <ref>Eric C. Schneider, Smack: Heroin and the American City, University of Pennsylvania Press, 2008, chapter one</ref>

Large scale international heroin production effectively ended in China with the victory of the communists in the civil war in the late 1940s.Template:Fact 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.

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 (former Burma), the heartland of the Golden Triangle remained the second largest producer of heroin, after Afghanistan.<ref name="Afghan_Burmese_heroin">Template:Cite web</ref>

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.<ref name="Afghan_Burmese_heroin">Template:Cite web</ref> 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.

[edit] Trafficking

See also: Opium production

Traffic is heavy worldwide, with the biggest producer being Afghanistan.<ref>Template:Cite web</ref> According to U.N. sponsored survey,<ref>Template:Cite web</ref> Template:As of, Afghanistan accounted for production of 87 percent of the world's heroin.<ref>Template:Cite web</ref>

The cultivation of opium in Afghanistan reached its peak in 1999, when 225,000 acres - 350 square miles - 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 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, with Afghanistan supplanting Burma to become the world's largest opium producer once more. <ref>OPIUM WARS WITHIN, Jackie Jura ~ an independent researcher monitoring local, national and international events ~ http://www.orwelltoday.com/afghanheroin.shtml</ref> 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.<ref>Template:Cite web</ref>

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 South-east 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, both in 2005.

[edit] Risks of use

 This article needs additional citations for verification.
Please help improve this article by adding reliable references. Unsourced material may be challenged and removed. (May 2007)
  • 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:
  • 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 or infectious diseases)<ref>Dettmeyer RB, Preuss J, Wollersen H, Madea B (January 2005). "Heroin-associated nephropathy". Expert Opin Drug Saf 4 (1): 19–28. doi:10.1517/14740338.4.1.19. PMID 15709895. </ref>

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.

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.<ref>Shane Darke, Deborah Zador (1996). "Fatal Heroin 'Overdose': a Review". Addiction 91 (12): 1765–1772. doi:10.1111/j.1360-0443.1996.tb03800.x. </ref> 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 give a figure of between 75 and 375 mg for a 75 kg being fatal for 50% of opiate naive people.<ref>Toxic Substances in water</ref> 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.<ref>The "heroin overdose" mystery and other occupational hazards of addiction, Schaffer Library of Drug Policy</ref>

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.<ref>József Gerevich, Erika Bácskai, Lajos Farkas, and Zoltán Danics (2005). "A case report: Pavlovian conditioning as a risk factor of heroin 'overdose' death". Harm Reduct J. 2 (11): 11. doi:10.1186/1477-7517-2-11. PMID 16042795. </ref>

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.<ref>Hill MD, Cooper PW, Perry JR (January 2000). "Chasing the dragon--neurological toxicity associated with inhalation of heroin vapour: case report". CMAJ 162 (2): 236–8. PMID 10674060. PMC:1232277. </ref><ref>Halloran O, Ifthikharuddin S, Samkoff L (May 2005). "Leukoencephalopathy from "chasing the dragon"". Neurology 64 (10): 1755. doi:10.1212/01.WNL.0000149907.63410.DA. PMID 15911804. </ref><ref>Offiah C, Hall E (February 2008). "Heroin-induced leukoencephalopathy: characterization using MRI, diffusion-weighted imaging, and MR spectroscopy". Clin Radiol 63 (2): 146–52. doi:10.1016/j.crad.2007.07.021. PMID 18194689. </ref> Symptoms include slurred speech and difficulty walking.

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.<ref>Template:Cite news</ref>

[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

Image:Heroin black tar.jpg
Black tar heroin

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, excessive yawning or sneezing, tears, rhinorrhea, sleep difficulties (insomnia), cold sweats, chills, severe muscle and bone aches; nausea and vomiting, diarrhea, cramps, and fever.<ref>Adult Health Advisor 2005.4: Narcotic Drug Withdrawal</ref> 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, (also known as "kicking the habit")). 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 occasionally another short-acting opioid and then slowly taper the dose.

In the second approach, benzodiazepines such as diazepam (Valium) may be recommended for opiate withdrawal especially if there is comorbid alcohol withdrawal. Benzodiazepines may temporarily ease the anxiety, muscle spasms, and insomnia associated with opioid withdrawal. The use of benzodiazepines must be carefully monitored because these drugs have a high risk of physical dependence as well as abuse potential and have little or no cross tolerance with opiates and thus are not generally recommended as a first line treatment strategy. Also, although very unpleasant, opioid withdrawal is seldom fatal, whereas complications related to withdrawal from benzodiazepines, barbiturates and alcohol withdrawal (such as psychosis, suicidal depression, 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. Diarrhoea 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 – 7 days.

Buprenorphine is another opioid that was recently licensed for opioid substitution treatment. As a μ-opioid receptor partial agonist, patients develop less tolerance to it than to heroin or methadone due to its partial activation of the opiate receptor. 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 or other full agonist opiates 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.<ref>Dean AJ, Bell J, Christie MJ, Mattick RP (December 2004). "Depressive symptoms during buprenorphine vs. methadone maintenance: findings from a randomised, controlled trial in opioid dependence". Eur. Psychiatry 19 (8): 510–3. doi:10.1016/j.eurpsy.2004.09.002. PMID 15589713. </ref>

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.<ref>Template:Cite web</ref> 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.

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.<ref> H.S. Lotsof. Ibogaine in the Treatment of Chemical Dependence Disorders: Clinical Perspectives. MAPS Bulletin 1995 V(3):19-26 </ref>

[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 heroin addicts doubled every sixteenth month during a period of ten years, 1959-1968.<ref>Nils Bejerot: The Swedish Addiction Epidemic in global perspective</ref> 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.<ref>Template:Cite web</ref>

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 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.<ref>Template:Cite web</ref> A national referendum in November 2008 showed 68% of voters supported the plan,<ref>Template:Cite news</ref> 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,<ref>Template:Cite web</ref> and Canadian<ref>Template:Cite web</ref> cities to try out their own heroin prescription programs.<ref>Nordt C, Stohler R (June 2006). "Incidence of heroin use in Zurich, Switzerland: a treatment case register analysis". Lancet 367 (9525): 1830–4. doi:10.1016/S0140-6736(06)68804-1. PMID 16753485. </ref> Some Australian cities (such as Sydney) have instituted legal heroin supervised injecting centers, in line with other wider harm minimization programs.

Starting in January 2009 Denmark is also going to prescribe heroin to a few addicts that have tried methadone and subutex without success.<ref> Template:Cite web </ref>

[edit] Controversy

It has been claimed that sustained use of heroin for as little as three days can cause withdrawal symptoms to appear if use is stopped, and the myth that "just one shot will hook you for life" has been one of the many sensationalist claims made about the drug. A belief in its overwhelming ability to addict anyone who tries it is one of the main justifications for heroin's continuing prohibition. The truth is that true physical dependence on heroin demonstrated by genuine physical withdrawal symptoms upon discontinuation of consumption (as opposed to a mental or psychological craving to repeat the heroin experience) is not acquired any faster than with continuous use of any other opiate, normally between three to six weeks in an opiate naive person. Many times patients in UK hospitals are treated with diamorphine daily for many weeks following painful surgery without experiencing any withdrawal upon discontinuation of the drug.<ref>David Shewan, Phil Dalgarno (2005). "Evidence for controlled heroin use? High levels of negative health and social outcomes among non-treatment heroin users in Glasgow" (PDF). British Journal of Health Psychology 10: 33–48. doi:10.1348/135910704X14582. </ref><ref>Template:Cite news</ref>

[edit] Popular culture

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[edit] Literature

  • Beat Generation author William S. Burroughs wrote about his experiences with heroin in numerous books, starting with the 1953 semi-autobiographical Junkie (aka Junky).
  • The Basketball Diaries is a 1978 book written by American author and musician Jim Carroll. It is an edited collection of the diaries he kept between the ages of twelve and sixteen. Set in New York City, they detail his daily life, sexual experiences, high school basketball career, Cold War paranoia, the counterculture movement, and, especially, his addiction to heroin, which began when he was 13. The book was made into a film under the same name in 1995 starring Leonardo DiCaprio.
  • Irvine Welsh's 1993 novel Trainspotting which was later made into a feature film under the same name explores the turbulent lives of an eccentric group of heroin users.
  • Allen Hoey's 2006 novel, Chasing the Dragon, examines the use of heroin among jazz musicians in the 1950s.
  • A 2007 book entitled The Heroin Diaries by author and musician Nikki Sixx from Mötley Crüe 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.
  • A 2008 book entitled "The Death Proclamation of Generation X: A Self-Fulfilling Prophesy of Goth, Grunge and Heroin" by researcher Maxim W. Furek investigates the prominence of heroin in music, motion pictures and Generation X culture. Published by i-Universe. ISBN 978-0-595-46319-0

[edit] Musicians who have used, or written about, heroin use

  • "The Needle and the Damage Done" is a song by Neil Young that chronicles the descent of musicians he knew into heroin addiction. It was written about the heroin use of his Crazy Horse guitarist Danny Whitten (before Whitten died of an overdose).
  • Jay-Z, in his song "I Know" from his 2007 American Gangster album wrote from the perspective of actually personifying the drug and how it interacts with and affects its users' and abusers' minds. From the same album came the single "Blue Magic", who's name is a direct reference to the kind of heroin that Frank Lucas sold in the movie American Gangster, the CD even came in a package similar to the one Lucas' heroin was sold in.
  • The song "H." by the band Tool is based on heroin addiction, although no members have been associated with using the drug.
  • Kurt Cobain of Nirvana was heavily addicted to heroin. His autopsy showed that he had a very high amount of heroin and other substances in his blood before he committed suicide.
  • Megadeth frontman Dave Mustaine is known for his past heroin drug abuse. The Megadeth song "Use the Man" talks about a musician who died of an overdose, as well as Mustaine's own heroin use.
  • The last song on Lamb of God's Sacrament album, "Beating on Death's Door," is said to be about the addicting grip heroin has on its users.
  • Alice in Chains frontman Layne Staley was also a well published heroin addict, right up to his death by overdose in April 2002. He wrote countless songs about his drug addiction including "God Smack", "Junkhead", and "Hate to Feel".
  • David Bowie's first single "Space Oddity," was seemingly about his experience 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."<ref name ="nuaa">Template:Cite web</ref>
  • The Depeche Mode single "Never Let Me Down Again" is believed to be a song about being on a heroin high. The members of Depeche Mode struggled with a heroin addiction and their 1994 Devotional Tour was at the height of that time.
  • The Stranglers' single "Golden Brown", from the late 1970s, is believed by some to be about a batch of brown heroin from Afghanistan that arrived in the UK around that time.
  • Bradley Nowell of Sublime wrote the songs "Badfish" and "Pool Shark", both of which deal with his heroin addiction. Nowell died of a heroin overdose in 1996.
  • Nikki Sixx wrote a song about his heroin addiction, which is included on the 1987 Motley Crue album "Girls, Girls, Girls" titled "Dancing on Glass". Sixx also wrote the hit "Kickstart My Heart" which was written about a Heroin overdose by Sixx. Sixx also wrote "The Heroin Diaries".
  • Suede recorded many songs about heroin. They have two songs which refer to lead singer Brett Anderson's addiction to the drug, and one simply called "Heroin", which features on their second LP Dog Man Star
  • The Used song, "Let It Bleed" refers to frontman Bert McCracken's heroin addiction before the band started.
  • 80s pop superstar Boy George used heroin. He also wrote and recorded a song of his experience with the drug titled "You Are My Heroin" in 1988.
  • Argentinian band Sumo's lead singer Luca Prodan, escaped from Europe to Argentina to get rid of his heroin addiction.
  • Philip Anselmo from Heavy Metal band Pantera overdosed on heroin after a show, inspiring the song "Death Rattle".
  • Pete Townshend suffered from heroin addiction in the 1980s. There are several passing references to heroin in his solo work, including "your love is like heroin" and "his pride is just like heroin".
  • Sid Vicious from the Sex Pistols died of a heroin overdose, and allegedly stabbed his girlfriend to death while both were strung out on heroin.
  • The Gun Club, LA based punk-rock group released the song "She's Like Heroin To Me" on their first album Fire of Love in 1981
  • System of a Down has songs refering to heroin. Such as "She's Like Heroin"
  • Bands Leftover Crack, Morning Glory and Choking Victim wrote about their heroin use in "Gimmie Heroin"

[edit] Film

  • Quentin Tarantino's 1994 film Pulp Fiction fully depicts the steps of heroin injection by Vincent Vega (John Travolta).
  • Darren Aronosfky's 2000 film Requiem for a Dream depicts the lives of a group of heroin addicts and the devastating results of their addiction.
  • The film Trainspotting, based on the book of the same name, revolves around a group of heroin users and the attempts of one of the group's efforts to quit.
  • The film RENT (2005), based on the musical by Jonathan Larson, includes a character, Mimi who struggles with a heroin addiction and has contracted AIDS from her usage.
  • The film Candy starring Heath Ledger focused on a couple very much in love and destroyed by heroin addiction.
  • Party Monster, a movie based on James St. James' true tales of New York City club kids in the late 1980s, shows an extreme use of heroin and other drugs such as ketamine (Special K) and cocaine.
  • The Film "Gia" based on a true story of model Gia Carangi is about her addiction and use of heroin and how it affected her.
  • The film "Christiane F." portraying the troubles of young heroin users in Berlin.
  • 1971's The Panic In Needle Park starring Al Pacino revolves around Pacino's character and his girlfriend's addictions to heroin and the repercussions of it. The film features graphic scenes of users injecting the drug.

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[edit] See also

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[edit] References

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[edit] Literature


[edit] External Links

Link to BIAdb Database

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