Heroin

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	C₂₁H₂₃N O₅
Molecular weight	369.42
Bioavailability	<35%
Metabolism	?
Elimination half life	3 minutes
Excretion	?
Pregnancy category	?
Legal status	Schedule I (USA); 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. Heroin is controlled under Schedules I and IV of the Single Convention on Narcotic Drugs [1]. It is not legal to manufacture, possess, or sell heroin in the United States, but diamorphine (heroin) is a legal prescription drug in the United Kingdom.

Heroin may be colloquially referred to as junk, smack, horse, brown sugar, babania, golden brown, black tar, montega, H, big H, lady H, dope, skag, juice, jude, diesel, boy, blows, pants, blow, left shoe, vrint, danger hat, or by a multitude of other slang terms. It is most commonly referred to as "gwasty the moon man".

History

Heroin was first synthesized in 1631 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 homeless people and black slaves … 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]

Heinrich Dreser, of Bayer in Elberfeld, Germany, noticed that diacetylmorphine was more potent than morphine. Bayer registered Heroin (meaning 'heroic treatment' from the German word heroisch) 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:

Other uses:

Contraindications:

Side effects:

Severe:

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:

Hepatological:

Liver disease (chronic use)

Hematological:

?

Musculo skeletal:

?

Neurological:

Analgesia

Psychological:

Respiratory:

Slow respiration
Shallow respiration
Pneumonia (chronic use)

Skin:

Itchiness
Flushing
Abscesses

Miscellaneous:

Heavy extremities

Heroin is a μ-opioid (mu-opioid) agonist. Like all drugs of its class, it binds to and activates endogenous μ-opioid receptors found in the brain, spinal cord and gut. As a medicine, it is administered usually in the form of its hydrochloride as an analgesic for severe pain. It is a Schedule I drug, making it illegal for any purpose in the United States, but it is legally used by cancer patients in the United Kingdom and other countries.

Heroin is also widely and illegally used as a powerful and addictive drug producing 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 which then binds with opioid receptors and produces the subjective effects of the heroin high. Heroin is therefore a prodrug. The onset of effects from heroin is dependent on the method of administration. Smoking and snorting heroin results in a rush within 10 to 15 minutes. Injecting heroin intravenously results in euphoria within 7 to 8 seconds, while injecting heroin intramuscularly takes longer, having an effect within 5 to 8 minutes.

Heroin acts on endogenous opioid receptors that are spread in discrete packets throughout the brain 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.

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 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 types of 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.

Production and trafficking

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 heroin from opium is a relatively simple process requiring only moderate technical know-how and common chemicals.

First morphine is isolated from the crude opium and then reacted with acetic anhydride, a chemical also used in the production of aspirin. 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.

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 Britain in the late 1700s, a move which helped to fuel the rise of the Chinese triad gangs that would eventually come to play a major role in the 20th century heroin trade.

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 world's opium 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.

Heroin use first appeared as a sub-cultural addiction problem in several countries in the early 20th century, but like the opium trade from which it developed, it was mainly restricted to small and fairly well-defined groups, such as Chinese migrants in western cities.

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. But, McCoy contends, the Mafia was able to gain control of the heroin trade thanks in large measure to 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, and that the Army wanted Luciano to provide their forces with local Mafia assistance during America's planned invasions of Sicily and Italy; in return the jailed mobster was allowed to run his operations unhindered from his cell, and he was deported back to Sicily after the war, where he oversaw a massive expansion in his organisation's drug operations before his death.

Luciano, who visited Vietnam, forged an alliance between his American Mafia family and the tough Corsican Mafia, establishing a wide-ranging heroin shipping, refining and distribution network based in the port town of Marseilles in France. He allegedly masterminded the network that was portrayed (semi-fictionally) in the film The French Connection.

Thanks to Corsican Mafia connections in the former French colony of Vietnam, the operation was able to forge new alliances with underworld forces there, and with triad gangs and organised crime figures in Hong Kong, Shanghai, New York City and Sydney. As opium production in Turkey waned, the Mafia established a lucrative new source of supply in the Golden Triangle region and funnelled the production out via South Vietnam. 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.

The battalions of American servicemen in Vietnam provided a perfect test market for the Asian syndicates, 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.

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, Great Britain 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

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.

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 alleges that the C.I.A. secretly collaborated with drug syndicates and was complicit in the expansion of the global heroin trade in the late 20th century, even though he has no evidence to back up his accusations. 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 1980's, Irangate 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 sacrified 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, 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

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.

Withdrawal symptoms

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 lachrymation, 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.

For those who repeatedly fail attempts at complete detoxification and relapse to heroin use, maintenance with regular doses of methadone is recommended. The newer alternative to methadone maintenance employs use of the drug buprenorphine.

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 used among addicts, combinations of stimulants and depressants can have unpredictable and sometimes fatal results.

Culture

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

External links

Books

Heroin (1998) ISBN 1568381530
Heroin Century (2002) ISBN 0415278996
This is Heroin (2002) ISBN 1860744249
The Heroin User's Handbook by Francis Moraes (paperback 2004) ISBN 1559502169
The Little Book of Heroin by Francis Moraes (paperback 2000) ISBN 0914171984

History

Usage and effects

Production and trafficking

Manufacturing

History

Trafficking

Risks of non-medical abuse of heroin

Withdrawal symptoms

Drug interactions

Culture

See also

External links

Books