Heroin

This article is an article about the drug heroin. For the Hardcore Emo band, see Heroin (band). For the Velvet Underground song, see Heroin (song). For a female hero, see Heroine.

Diamorphine chemical structure Diacetylmorphine
IUPAC name: (5α,6α)-7,8-didehydro-4,5-epoxy- 17-methylmorphinan-3,6-diol diacetate (ester)
CAS number 561-27-3	ATC code N02AA09
Chemical formula	C21H23NO5
Molecular weight	369.42
Bioavailability	<35%
Metabolism	?
Elimination half life	3 minutes
Excretion	?
Pregnancy category	?
Legal status	Schedule I (U.S.); Class A (UK)
Delivery	Vaporized, insufflated, injected, ingested

Heroin or diacetylmorphine (INN) is a semi-synthetic opioid. It is the 3,6-diacetyl derivative of morphine (hence diacetylmorphine) and is synthesised from it by acetylation. The white crystalline form is commonly the hydrochloride salt, diacetylmorphine hydrochloride. It is highly addictive when compared to other substances, although occasional use without symptoms of withdrawal has been noted. Internationally, Heroin is controlled under Schedules I and IV of the Single Convention on Narcotic Drugs [1]. It is illegal to manufacture, possess, or sell heroin in the United States but, under the name diamorphine, heroin is a legal prescription drug in the United Kingdom. Popular street names for heroin include dope, diesel, smack, scag and H.

History

Bayer Heroin (TM)

Bayer Heroin bottle.

Heroin was first synthesized in 1874 by C.R. Alder Wright, a British chemist working at St. Mary's Hospital Medical School, London. 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. We now call it diacetylmorphine. The compound was sent to F.M. Pierce of Owens College, Manchester, for analysis. He 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 dilated, 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) [2]

Felix Hoffmann, of Bayer in Elberfeld, Germany created Heroin as a medicine 11 days after inventing Aspirin. Afraid of the possible side effects of Aspirin, Bayer registered Heroin (meaning 'heroine' in German, chosen because in field studies people using the medicine felt 'heroic') as a trademark. From 1898 through to 1910 it was marketed as a non-addictive morphine substitute and cough medicine for children. As with Aspirin, Bayer lost some of its trademark rights to Heroin following World War I.

In 1914 the Harrison Narcotics Tax Act made it illegal to manufacture or possess heroin in the United States.

Usage and effects

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

Contraindications: Alcohol Barbiturates Stimulants Other opioids

Side effects: Severe: Respiratory arrest Spontaneous abortion Atypical sensations: ? Cardiovascular: Lowered heart rate Infection of heart lining and valves (chronic use) Ear, nose, and throat: Dry mouth Endocrinal: ? Eye: Pupil constriction Gastrointestinal: Nausea Constipation Hepatological: Liver disease (chronic use) Hematological: ? Musculoskeletal: ? Neurological: Analgesia Psychological: Confusion Euphoria Sedation Respiratory: Slow respiration Shallow respiration Pneumonia (chronic use) Skin: Itchiness Flushing Abscesses Miscellaneous: Heavy extremities

In the United States, heroin is a Schedule I drug and is illegal for any purpose. In the United Kingdom heroin is available on prescription, though it is a restricted Class A drug. According to the British National Formulary edition 50, 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. In comparison to morphine, it may cause less nausea and hypotension and can be dissolved in a smaller quantity of liquid.

The late serial killer and general practitioner Harold Shipman obtained large quantities of diamorphine by writing prescriptions for his cancer patients and keeping the drugs. Shipman was convicted of killing 15 patients with diamorphine, though an enquiry later estimated 340 were murdered.

Heroin is also widely and illegally used as a powerful and addictive drug that produces intense euphoria, which often disappears with increasing tolerance. Although many other μ-opioid agonists (e.g., morphine) can produce essentially the same effects, it is thought that heroin's popularity with recreational users comes from its especially rapid onset. This in turn comes from its high lipid solubility provided by the two acetyl groups, resulting in a very rapid penetration of the blood-brain barrier after use. Heroin can be taken or administered in a number of ways, including snorting it and injecting it. It may also be smoked by inhaling the vapors produced when heated from below (known as "chasing the dragon"). Once in the brain, heroin is rapidly metabolized into morphine by removal of the acetyl groups. It is the morphine molecule that then binds with opioid receptors and produces the subjective effects of the heroin high. Heroin is therefore a prodrug. The onset of heroin's effects is dependent on the method of administration. Orally the heroin is totally metabolized in vivo into morphine before crossing the blood-brain barrier, so the effects are the same as morphine when taken by mouth. Snorting heroin results in onset within 10 to 15 minutes. Smoking heroin results in a rush within 2-5 minutes. Intravenous injection results in rush and euphoria within 7 to 8 seconds, while intramuscular injection takes longer, having an effect within 5 to 8 minutes.

Heroin is a μ-opioid (mu-opioid) agonist. It acts on endogenous μ-opioid receptors that are spread in discrete packets throughout the brain, spinal cord and gut in almost all mammals. Heroin, along with other opioids, are agonists to four endogenous neurotransmitters. They are β-endorphin, dynorphin, leu-enkephalin, and met-enkephalin. The body responds to heroin in the brain by reducing (and sometimes stopping) production of the endogenous opioids when heroin is present. Endorphins are regularly released in the brain and nerves and attenuate pain. Their other functions are still obscure, but are probably related to the effects produced by heroin besides analgesia (antitussin, anti-diarrheal). The reduced endorphin production in heroin users creates a dependence on the heroin, and the cessation of heroin results in the extreme symptoms including pain (even in the absence of physical trauma). This set of symptoms is called withdrawal syndrome. It has an onset 6 to 8 hours after the last dose of heroin.

Production and trafficking

Primary worldwide producers of heroin.

Manufacturing

Heroin is produced for the black market through opium refinement processes. Unlike drugs such as LSD, the production of which requires considerable expertise in chemistry and access to constituents which are now tightly controlled, the refinement of the first three grades of heroin from opium is a relatively simple process requiring only moderate technical know-how and common chemicals. The final grade of heroin favored in the west is more difficult to produce and involves a potentially dangerous chemical procedure.

First morphine is isolated from the crude opium (through being dissolved in water, reacted with lime fertilizer such that it precipates out, and then reacted again with ammonia; what is left is then mechanically filtered to yield a final product of morphine weighing about 90% less than the original quantity of opium). The morphine is reacted with acetic anhydride — a chemical also used in the production of aspirin — in the complicated five-step process used by most refineries in the Golden Triangle. The first step is to cook the morphine at 85°C (185°F) for six hours with an equivalent weight of acetic anhydride. In the second, a treatment of water and hydrochloric acid then purifies the product moderately. When the chemists add sodium carbonate, the particulates settle. Step four involves the heroin being heated in a mixture of alcohol and activated charcoal until the alcohol evaporates. The fifth step is optional, as it only changes the heroin into a finer white powder, more easily injectable; this so-called "no. 4 heroin" is principally exported to the Western markets. In this last, most dangerous step, the heroin (after being dissolved in alchohol), percipates out in tiny white flakes when a mixture of ether and hydrochloric acid is injected; the reason for the danger is that the ether could well explode, leveling or severely damaging the refinery (as has happened to a number of such facilities).

The purity of the extracted morphine determines in large part the quality of the resulting heroin. Most black market heroin is highly impure due to contaminants left after refinement of opium into morphine which then remain in the final product; even if the final product is in the upper range of purity (80 - 99% pure), when the final product reaches the addict, it typically has been cut multiple times, and its purity is down to less than 5%.

History

The origins of the present international illegal heroin trade can be traced back to the forcible imposition of the opium trade on China by the United Kingdom in the late 1700s. The opium trade sparked the two Opium Wars that resulted in a series of Unequal Treaties that ceded Hong Kong to the United Kingdom in mid 19th century. Later in the 20th century, Chinese triad gangs would eventually come to play a major role in the heroin trade, most of which are based in Hong Kong and Southern China.

Although it remained legal in some countries until after World War II, the anti-drug activism of the United States led most western countries to declare heroin a controlled substance in the latter half of the 20th century.

Prior to the 1970s, much of the opium consumed in the west was grown in Turkey, but in the late Sixties, under pressure from the U.S. and the United Nations, Turkey agreed to eliminate its opium production, leading to the development of a major new cultivation and refining base in the so-called "Golden Triangle" region in South East Asia in the late 1960s.

Although it was beginning to become more prevalent by the 1930s, Asian historian and drug traffic expert Dr Alfred W. McCoy reports that heroin trafficking was virtually eliminated in the U.S. during World War II due to temporary trade disruptions caised by the war. McCoy contends the Mafia was able to gain control of the heroin trade thanks in large measure due to the unintended consquences of a covert deal between top Mafia leader Lucky Luciano and American military intelligence.

McCoy claims that Luciano was asked to provide Mafia assistance in rooting out communist and/or Nazi influence on the waterfronts. Other historians have suggested that the US in reality gave in to Mafia extortion and that the Mafia itself was the threat to the waterfront. Later, the US Army wanted Luciano to provide their forces with local Mafia assistance during America's planned invasion of Sicily. The end result was the US Army ended up unintentionally handing control over Sicily to the Mafia. Luciano was eventually released from prison and moved back to Sicily where he was able to construct a series of large-scale heroin factories The Network eventually spread out into other areas of southern europe. Luciano arranged, for example, a deal with the Corsican Mafia operating out of Marseilles in France. He allegedly masterminded the creation of the network that was portrayed (semi-fictionally) in the film The French Connection. The Corsican Mafia in Marseilles were used by the US and French governments as a force to counter-balance the strong communist movement in the South of France after the war.

In southeast asia, the governments of most countries and many colonial officials had been involved in the opium trade for a very long time. Thanks to Corsican Mafia connections in the former French colony of Vietnam, Luciano was able to begin to develop Southeast Asia as a new source of Opium even as Turkish and Iranian production declined. The Vietnam War had the unintended consquence of first opening up many areas of Southeast Asia to modern transportation and then presenting a ready-made market for the drug among the U.S. military personnel stationed in the region.

McCoy's most controversial assertion is that the C.I.A. pursued a policy, which he describes as "radical pragmatism", and that in the name of the fight against Communism, the Agency was covertly making expedient alliances with local warlords, Mafiosi and corrupt South Vietnamese officials. His critics are not convinced that the actions were those of the agency rather than the actions of individuals. They also point out that North Vietnamese and Viet Cong officials were equally complicit in the trade. Indeed, it is difficult to find anyone during the war who was not participating in some way. The CIA and the war indirectly allowed many things to happen in southeast asia that might have otherwise not occured, but that is far different than a government conspiracy intended to bring those things about.

The real turning point came in 1970-71 when the first high-grade heroin laboratories opened in the golden triangle. Prior to this, the chemical skills for refinement had existed only in europe. This event changed the entire world of heroin in that it allowed the opium producers control over the creation of the final product. The hundreds of thousands of American servicemen in Vietnam provided a perfect market for the heroin producers, and heroin use among soldiers rapidly reached near-epidemic proportions in 1970-71, with some unit medical officers reporting that as many as 15% percent of G.I.s in some units were regular users. The money from this huge American market for Heroin flooded into the hands of warlords in the region and allowed them to self-finance ever-larger activies.

In 1971 the first large consignments of South East Asian heroin were intercepted in Europe and America, and by the mid-1970s heroin addiction fulfilled its promise as a serious social problem in the United States (where it had already been growing in street traffic throughout the late 1950s and 1960s), Australia, the United Kingdom, and many other nations, notably among youth and particularly in the African-American population in the U.S. Based on the success of this network, organised crime groups began to establish illegal trades in other highly addictive drugs, notably cocaine.

Trafficking

Asian heroin

Traffic is heavy worldwide, with the biggest producer being Afghanistan, which after years of war and poverty is now an area ripe for opium growing. A 60 Minutes report claims that 87 percent of the world's heroin supply comes from Afghanistan.

File:Balininelawrenceevidence.jpg

Heroin concealed under the clothes of a drug smuggler.

Some observers, particularly political conservatives in the United States, have accused China of being a leading producer of heroin, but evidence in support of this is questionable. Conversely, some radical critics have pointed the finger at the United States, citing the work of Dr. Alfred W. McCoy, who has shown that the C.I.A. secretly collaborated with Asian drug syndicates and was complicit in the expansion of the global heroin trade in the late 20th century in order to prosecute the Cold War and support various Souteast Asian regimes. The "French Connection" and Lucky Luciano's role are cited as examples. Reporter Gary Webb, who was found dead in 2004, maintained that the crack epidemic was related to U.S. governmental agencies.

In the 1980s, the Iran-Contra Affair led to a 1988 report from the Subcommittee on terrorism, narcotics and international operations, led by Sen. John Kerry, which proved contra-drugs links, including what he deemed "one of the most serious foreign policy failures for the United States", Manuel Noriega's U.S. support. "Narcotic law enforcement has often taken a back seat to other diplomatic and national security archives. The war on drugs must not in the future be sacrificed to other foreign policy considerations," stated the report [3].

Heroin is one of the most profitable illicit drugs since it is compact and easily concealed. At present, opium poppies are mostly grown in the Middle East, India, and Afghanistan, and in Asia, especially in the region known as the Golden Triangle straddling Myanmar, Thailand, Vietnam, Laos and Yunnan province in 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 as 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.

Conviction for trafficking in heroin in many countries, including Malaysia, Indonesia, Taiwan, Thailand and Singapore, carries the death penalty. 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 Australian citizen Van Tuong Nguyen in Singapore, both in 2005.

Risks of non-medical abuse of heroin

• Overdose, sometimes fatal
• For intravenous abusers (people who inject) of heroin, the use of non-sterile needles and syringes and other materials leads to the risk of contracting blood-borne pathogens such as HIV and/or hepatitis infections as well as the risk of contracting bacterial or fungal endocarditis
• Poisoning from contaminants added to "cut" or dilute heroin
• Chronic constipation
• Venous sclerosis

Many countries and local governments have instituted programs to supply sterile needles to people who inject illegal drugs in order to reduce some of these contingent risks. While needle exchanges have demonstrated an immediate public health benefit, some see such programs as tacit acceptance of illicit drug use. The United States does not support needle exchanges federally by law, though some of its state and local governments do.

A heroin overdose is usually treated with an opioid antagonist, such as naloxone (Narcan) or naltrexone, which have a high affinity for opioid receptors but do not activate them. This blocks heroin and other opioid agonists and causes an immediate return of consciousness and start of withdrawal symptoms when administered intraveneously. The half-life of these antagonists is usually much shorter than that of the opiate drugs they are used to block, so the antagonist usually has to be re-administered multiple times until the opiate has been metabolized by the body.

Contrary to popular belief, a heroin overdose is not fast-acting. Stories about people who "OD with the needle still in their arm" and the like are not attributable to heroin overdoses, but rather they are very often the result of a fatal reaction with the adulterant. Quinine is notorious for causing such deaths. In the case of an actual heroin overdose, it very often takes many hours to die.

Heroin overdoses are more rare than one might first expect. As noted above, an overdose is immediately reversible with an opioid antagonist injection. The overwhelmingly vast majority of reported heroin overdoses are actually adulterant poisonings or fatal interactions with alcohol or methadone. True overdoses are rare because the LD₅₀ for a person already addicted is prohibitively high, to the point that there is no general medical consensus on where to place it. Several studies done in the 1920s gave addicts doses of 1,600–1,800 mg of heroin in one sitting, and no adverse effects were reported. This is approximately 160–180 times a normal recreational dose. Even for a non-addict, the LD₅₀ can be credibly placed above 350 mg.

It should be noted, however, that street heroin is of widely varying and unpredictable purity. This means that an addict may prepare what they consider to be a moderate dose while actually taking far more than intended. Also, relapsing addicts after a period of abstinence have tolerances below what they were during active addiction. If a dose comparable to their previous use is taken an overdose often results.

A final source of overdose in addicts comes from place conditioning. Heroin use, like other drug abuse behaviors is highly ritualized. While the mechanism has yet to be clearly elucidated, it has been shown that longtime heroin users, immediately before injecting in a common area for heroin use, show an acute increase in metabolism and a surge in the concentration of opiate-metabolizing enzymes. This acute increase, a reaction to a location where the addict has repeatedly injected heroin, imbues the addict with a strong (but temporary) tolerance to the toxic effects of the drug. When the addict injects in a different location, this place-conditioned tolerance does not occur, giving the addict a much lower-than-expected ability to metabolize the drug. 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.

Withdrawal

Black tar heroin

The withdrawal syndrome from heroin (or any other short-acting opioid) can begin within 6 hours of discontinuation of sustained use of the drug: sweating, malaise, anxiety, depression, persistent and intense penile erection in males (priapism), general feeling of heaviness, cramp-like pains in the limbs, yawning and lacrimation, sleep difficulties, cold sweats, chills, severe muscle and bone aches not precipitated by any physical trauma, nausea and vomiting, diarrhea, gooseflesh (hence, the term "cold turkey"), cramps, and fever occur. Many addicts 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 causes muscle spasms in the legs of the user (restless leg syndrome), hence the term "kicking the habit". However, it must be noted that each person's symptoms can be unique. Users seeking to take the "cold turkey" (without any preparation or accompaniments) approach are generally more likely to experience the negative effects of withdrawal in a more pronounced manner.

Two general approaches are available to ease 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. The other approach, which can be used alone or in combination, is to relieve withdrawal symptoms with non-opioid medications.

In the second approach, benzodiazepines such as diazepam (Valium) ease the often extreme anxiety of opioid withdrawal. The most common benzodiazepine employed as part of the detox protocol in these situations is oxazepam (Serax). However, it is important to note that benzodiazepine use may also lead to a dependence, and many opiate addicts also abuse other central nervous system depressants including benzodiazepines and barbituates. Also, though unpleasant, opiate withdrawal seldom has potential to become fatal, whereas complications related to withdrawal from benzodiazepines, barbiturates and alcohol (such as seizures, cardiac arrest, and delirium tremens) can prove hazardous and potentially fatal. Many symptoms of opioid withdrawal are due to rebound hyperactivity of the sympathetic nervous system, and this can be suppressed with clonidine (Catapres), a centrally-acting alpha-2 agonist primarily used to treat hypertension.

Buprenorphine is one of the most recent opioid agonist/antagonist used for treating addiction. It develops tolerance much slower than heroin or methadone. It also has a withdrawal many times softer than heroin and other opioids. It can be admnistered up to every 24-48 hrs. By itself buprenorphine has low overdose dangers. Buprenorphine is a kappa-opioid receptor antagonist. This gives the drug an anti-depressant effect, increasing physical and intellectual activity. Buprenorphine also acts as a partial agonist at the same μ-receptor illicit opiates such as Heroin initiate from. Due to its effects on this receptor, patients are unable to obtain any "high" from other opiates during buprenorphine treatment.

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. [4] A sustained-release formulation would allow for easier administration and adherance to treatment, and reduce the risk of diversion or misuse.

Methadone is another μ-opioid agonist often used to substitute for heroin in treatment for heroin addiction. Compared to heroin, methadone is well (but slowly) absorbed orally and has a much longer duration of action. Thus methadone maintenance avoids the rapid cycling between intoxication and withdrawal associated with heroin addiction. In this way, methadone has shown some success as a "less harmful substitute"; despite being much more addictive than heroin, and is recommended for those who have repeatedly failed to complete detoxification. As of 2005, the μ-opioid agonist buprenorphine is also being used to manage heroin addiction, being a superior, though still imperfect and not yet widely known alternative to methadone. Note that methadone, since it is longer-acting, produces withdrawal symptoms that are usually less severe and that appear later than with heroin, but may last longer.

Researchers have discovered two other opioid antagonists: naloxone and the longer-acting naltrexone. These two medications block the effects of heroin, as well as the other opioids at the receptor site. Recent studies have suggested that the addition of naloxone and naltrixone may improve the success rate in treatment programs when combined with the traditional therapy.

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 immunised monkeys had an increase in dose of x16, their antibodies became saturated and the monkey had the same effect from heroin as non-immunised monkeys. Secondly, until they reached the x16 point immunised monkeys would substitute other drugs to get a heroin-like effect. These factors suggested that immunised human addicts would simply either take massive quantities of heroin, or switch to other hard drugs, which is known as cross-tolerance.

There is also a controversial treatment for heroin addiction based on an African drug, ibogaine. Many people travel abroad for ibogaine treatments that generally stop the addiction for 3 months or more.

Drug interactions

Opiates are strong central nervous system depressants, but regular users develop physiological tolerance allowing gradually increased dosages. In combination with other central nervous system depressants, heroin may still kill experienced users.

Toxicology studies of heroin-related deaths reveal frequent involvement of other central nervous system depressants, including alcohol, benzodiazepines such as diazepam (valium), and occasionally methadone. Ironically, benzodiazepines and methadone are often used in the treatment of heroin addiction.

Cocaine also proves to be often 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.

Culture

Main article: Heroin in popular culture

Heroin has inspired countless writers, musicians and other artists over the past century of use.

See also

• Black Tar Heroin
• Hillbilly heroin
• China White
• Methadone
• Recreational drug use
• Psychoactive drug
• Scag
• List of people known to be addicted to opiates
• List of famous drug smugglers
• Opium
• Poppy

References

• Heroin (1998) ISBN 1-568-38153-0
• Heroin Century (2002) ISBN 0-415-27899-6
• This is Heroin (2002) ISBN 1-860-74424-9
• The Heroin User's Handbook by Francis Moraes (paperback 2004) ISBN 1-559-50216-9
• The Little Book of Heroin by Francis Moraes (paperback 2000) ISBN 0-914-17198-4
• Heroin: A True Story of Addiction, Hope and Truimph by Julie O'Toole (paperback 2005) ISBN 1-905-37901-3

External links

• 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)
• The Good Drugs Guide - Heroin
• From Flowers to Heroin, CIA publication.
• The mismanagement of methadone
• Harrowing Heroin by Geoff Morton
• National Alliance of Advocates for Buprenorphine Treatment - non-profit education website for treatment of Heroin addiction
• "The Orthomolecular Treatment of Drug Addiction" by Archie Kalokerinos M.D.
• NIDA InfoFacts on Heroin
• ONDCP Drug Facts
• Role of Government of Pakistan in Narcotics Control
• 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