Heroin
Heroin, or diacetylmorphine (INN), also known as diamorphine (BAN), is a semi-synthetic opioid drug synthesized from morphine, a derivative of the opium poppy. It is the 3,6-diacetyl ester of morphine (di (two)-acetyl-morphine). The white crystalline form is commonly the hydrochloride salt diacetylmorphine hydrochloride, however heroin freebase is typically a white powder.
As with other opioids, heroin is used as both a pain-killer and a recreational drug and has an extremely high potential for abuse. Frequent and regular administration is associated with tolerance, moderate physical dependence, and severe psychological dependence which develops into addiction.
Bayer named its new over the counter drug “Heroin” in 1898. Because Bayer is a German company, the name was most likely derived from the common German word “heroisch” (heroic), related to the Greek ἡρως, “hero.” The name originated from to its perceived effects on a user or its intention as a powerful (”heroic”) painkiller. It was also developed as a morphine substitute that did not have its addictive side-effects. Contrary to Bayer’s advertising as a non-addictive morphine substitute, its new drug, Heroin would cause an addiction worse than any drug ever previously known.
The opium poppy was cultivated in lower Mesopotamia as long ago as 3400 BC. The chemical analysis of opium in the 19th century revealed that most of its activity could be ascribed to two alkaloids, codeine and morphine. Diacetylmorphine was first synthesized in 1874 by C. R. Alder Wright, an English chemist working at St. Mary’s Hospital Medical School in London. He had been experimenting with combining morphine with various acids. He boiled anhydrous morphine alkaloid with acetic anhydride for several hours and produced a more potent, acetylated form of morphine, now called diacetylmorphine.
Wright’s invention did not lead to any further developments, and diacetylmorphine only became popular after it was independently re-synthesized 23 years later by another chemist, Felix Hoffmann. Hoffmann, working at the Aktiengesellschaft Farbenfabriken (today the Bayer pharmaceutical company) in Elberfeld, Germany, was instructed by his supervisor Heinrich Dreser to acetylate morphine with the objective of producing codeine, a constituent of the opium poppy, pharmacologically similar to morphine but less potent and less addictive. Instead the experiment produced an acetylated form of morphine one and a half to two times more potent than morphine itself.
From 1898 through to 1910 diacetylmorphine was marketed under the name heroin as a non-addictive morphine substitute and cough suppressant. Bayer marketed heroin as a cure for morphine addiction before it was discovered that it rapidly metabolizes into morphine. As such, heroin is essentially a quicker acting form of morphine. The company was embarrassed by the new finding, which became a historic blunder for Bayer.
In the U.S.A. the Harrison Narcotics Tax Act was passed in 1914 to control the sale and distribution of “heroin” and other opioids, which allowed the drug to be prescribed and sold for medical purposes. In 1924 the United States Congress banned its sale, importation or manufacture. It is now a Schedule I substance, which makes it illegal for non-medical use in signatory nations of the Single Convention on Narcotic Drugs treaty, including the United States. Later, as with Aspirin, Bayer lost some of its trademark rights to “heroin” under the 1919 Treaty of Versailles following the German defeat in World War I.
Pharmacology
When taken orally, diacetylmorphine undergoes extensive first-pass metabolism via deacetylation, making it a prodrug for the systemic delivery of morphine. 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. 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. 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.
Both morphine and 6-MAM are μ-opioid agonists which bind to receptors present throughout the brain, spinal cord and gut of all mammals. The μ-opioid receptor also binds endogenous opioid peptides such as β-endorphin, Leu-enkephalin, and Met-enkephalin. Repeated use of diacetylmorphine results in a number of physiological changes, including decreases in the number of μ-opioid receptors. These physiological alterations lead to tolerance and dependence, so that cessation of diacetylmorphine use results in a set of 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. The contribution of these receptors to the overall pharmacology of heroin remains unknown.
The medical use of diamorphine (in common with other strong opioids such as morphine, fentanyl and oxycodone) is controlled in the United Kingdom by the Misuse of Drugs Act 1971. In the UK, it is a class A controlled drug. Registers of its use are required to be kept in hospitals. Heroin is also used as a maintenance drug in the treatment of heroin addicts. Though this is somewhat controversial among proponents of a zero tolerance drug policy it has proven superior to methadone in improving the social and health situation of addicts.
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. 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. 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.
One of the most common methods of illicit heroin 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.
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. Large doses of heroin can cause fatal respiratory depression, and the drug has been used for suicide or as a murder weapon. The serial killer Dr Harold Shipman used it on his victims as did Dr John Bodkin Adams (see his victim, Edith Alice Morrell). Because significant tolerance to respiratory depression develops quickly with continued use and is lost just as quickly during withdrawal, it is often difficult to determine whether a heroin death was an accident, suicide or murder. Examples include the overdose deaths of Sid Vicious, Janis Joplin, Tim Buckley, Layne Staley, Bradley Nowell, Ted Binion, and River Phoenix.
Effects
1). Data from The Lancet shows heroin to be the most addictive and most harmful of 20 drugs.
Central nervous system:
• Drowsiness
• Disorientation
• Delirium
Neurological:
• Analgesia
• Tolerance
• Addiction (Physical Dependence)
2). Main long-term effects of usage.
Psychological:
• Addiction (Psychological Dependence)
• Anxiolysis
• Confusion
• Euphoria
• Somnolence
3). Main short-term effects of heroin usage.
Cardiovascular & Respiratory:
• Bradycardia
• Hypotension
• Hypoventilation
• Shallow breathing
• Respiratory depression
Gastrointestinal:
• Nausea
• Vomiting (protracted)
• Constipation
• Dyspepsia
Musculoskeletal:
• Analgesia
• Ataxia
• Muscle spasticity
Skin:
• Itching
• Flushing/Rash
Miscellaneous:
• Dry mouth (Xerostomia)
• Miosis, or pupil constriction (”pinpoint pupils”)
• Urinary retention
Recreational uses:
• Euphoria
• Relaxation
Medicinal uses:
• Powerful analgesic
• Cough suppressant
• anti-diarrheal
Contraindications:
• Alcohol
• Barbiturates and Benzodiazepines
• Stimulants
• Other opioids (depends heavily on tolerance)
Regulation
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.
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 €35-40 per gram. The price of white heroin is reported only by a few European countries and ranged between €27 and €110 per gram.
The United Nations Office on Drugs and Crime claims in its 2008 World Drug Report that typical US retail prices are US$172 per gram.
Production and trafficking:
The Golden Triangle
• Primary worldwide producers of heroin.
• Manufacturing
• Heroin, also known as diacetyl morphine is produced from acetylation of morphine derived from natural opium sources. Numerous mechanical and chemical means are used to purify the final product. The final product have different appearance depending on purity and have different names.
History of heroin traffic:
The origins of the present international illegal heroin trade can be traced back to laws passed in many countries in the early 1900s that closely regulated the production and sale of opium and its derivatives including heroin. At first, heroin flowed from countries where it was still legal into countries where it was no longer legal. By the mid-1920s, heroin production had been made illegal in many parts of the world. An illegal trade developed at that time between heroin labs in China (mostly in Shanghai and Tianjin) and other nations. The weakness of government in China and conditions of civil war enabled heroin production to take root there. Chinese triad gangs eventually came to play a major role in the heroin trade. The French Connection route started in the 1930s.
Heroin trafficking was virtually eliminated in the U.S. during World War II due to temporary trade disruptions caused by the war. Japan’s war with China had cut the normal distribution routes for heroin and the war had generally disrupted the movement of opium.
After World War II, the Mafia took advantage of the weakness of the postwar Italian government and set up heroin labs in Sicily. The Mafia took advantage of Sicily’s location along the historic route opium took westward into Europe and the United States.
Large scale international heroin production effectively ended in China with the victory of the communists in the civil war in the late 1940s. The elimination of Chinese production happened at the same time that Sicily’s role in the trade developed. Although it remained legal in some countries until after World War II, health risks, addiction, and widespread recreational use led most western countries to declare heroin a controlled substance by the latter half of the 20th century.
In late 1960s and early 70s, the CIA supported anti-Communist Chinese Nationalists settled near Sino-Burmese border and Hmong tribesmen in Laos. This helped the development of the Golden Triangle opium production region, which supplied about one-third of heroin consumed in US after 1973 American withdrawal from Vietnam. As of 1999, Myanmar (formerly Burma), the heartland of the Golden Triangle remained the second largest producer of heroin, after Afghanistan.
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. 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.
Trafficking
Traffic is heavy worldwide, with the biggest producer being Afghanistan. According to U.N. sponsored survey, as of 2004, Afghanistan accounted for production of 87 percent of the world’s heroin. 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. 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.
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,
Risks of Use
For intravenous users of heroin (and any other substance), the use of non-sterile needles and syringes and other related equipment leads to several serious risks:
• the risk of contracting blood-borne pathogens such as HIV and hepatitis
• the risk of contracting bacterial or fungal endocarditis and possibly venous sclerosis
• abscesses
• Poisoning from contaminants added to “cut” or dilute heroin
• Chronic constipation
• Addiction and increasing tolerance
• Physical dependence can result from prolonged use of all opioids, resulting in with- drawal symptoms on cessation of use
• Decreased kidney function (although it is not currently known if this is due to
adulterants or infectious diseases)
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. 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. 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. 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.
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. 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.
Harm reduction
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).
Withdrawal
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.