Heroin

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).[4] 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 (probably from heroisch, German for heroic, 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. Bayer marketed heroin as a "cure" for morphine addiction before it was discovered that heroin is converted to morphine in the liver. All opiates are converted by the human liver into the identical molecule with varying degrees of concentration in the blood stream. The company felt somewhat embarrassed by this new finding and it became a historical blunder for Bayer [1]. As with aspirin, Bayer lost some of its trademark rights to heroin following World War I.

In the United States in 1914 the Harrison Narcotics Tax Act was passed to control the sale and distribution of heroin. The law still allowed heroin to be prescribed and sold for medical purposes. In particular, addicts could often still be legally supplied with heroin. In 1924, the United States Congress passed additional legislation banning the sale, importation or manufacture of heroin in the United States.

Use
In the United Kingdom heroin is available on prescription, though it is a restricted Class A drug. According to the British National Formulary (BNF) edition 50, diamorphine hydrochloride may be used in the treatment of acute pain, myocardial infarction, acute pulmonary edema, 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, hypotension, sedation, euphoria and can be dissolved in a smaller quantity of liquid.

Heroin is also widely and illegally used as a powerful and addictive drug that produces intense euphoria, which often disappears with increasing tolerance. It is thought that heroin's popularity with recreational users, compared to morphine or other opiates, comes from its somewhat different perceived effects.[5] 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 an almost immediate, though mild effect which strengthens the longer it is used in that particular session. 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 extremely uncomfortable 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.

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 expertise 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 precipitates 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 heating the heroin 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 alcohol), precipitates out in tiny white flakes when a mixture of ether and hydrochloric acid is injected; this step is dangerous due to the fact that the ether may 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), once it reaches the consumer, it typically has been cut multiple times.

Trafficking
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 Tientsin) and other nations. The weakness of government in China and conditions of civil war enabled heroin production to take root there. Chinese triad gangs eventually came to play a major role in the heroin trade.

Heroin trafficking was virtually eliminated in the U.S. during World War II due to temporary trade disruptions caused by the war. Japan's war with China had cut the normal distribution routes for heroin and the war had generally disrupted the movement of opium. After the second world war, the Mafia took advantage of the weakness of the postwar Italian government and set up heroin labs in Sicily. The Mafia took advantage of Sicily's location along the historic route opium took from Iran westward into Europe and the United States. Large scale international heroin production effectively ended in China with the victory of the communists in the civil war in the late 1940s. The elimination of Chinese production happened at the same time that Sicily's role in the trade developed.

Although it remained legal in some countries until after World War II, health risks, addiction, and widespread abuse led most western countries to declare heroin a controlled substance by the latter half of the 20th century.

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

After the overthrow of the Shah of Iran, the new Iranian regime was much more tolerant of opium production. At the same time, the Soviet-Afghan war led to increased production in the Pakistani-Afghani border regions. Both events led to increased international production of heroin at lower prices in the 1980s. The trade shifted away from Sicily in the late 1970s as various criminal organizations violently fought with each other over the trade. The fighting also led to a stepped up government law enforcement presence in Sicily. All of this combined to greatly diminish the role of the country in the international heroin trade.

Modern Trafficking
Traffic is heavy worldwide, with the biggest producer being Afghanistan. According to U.N. sponsored survey [2], as of 2004, Afghanistan accounted for production of 87 percent of the world's heroin. [3] 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. [4]

Heroin concealed under the clothes of a drug smuggler.Dr. Alfred W. McCoy has claimed that the C.I.A. secretly collaborated with Asian drug syndicates and was complicit in the expansion of the global heroin trade from 1970 to 1973 in order to prosecute the Cold War. While the Vietnam War brought modern transportation to remote opium areas, McCoy himself does not claim that the CIA set up the drug labs in Southeast Asia or created the trade. [citation needed]

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, Pakistan, 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 one of the biggest opium-growing countries. However, the efforts of Pakistan's Anti-Narcotics Force have since reduced the opium growing area by 59% as of 2001[citation needed]. Some suggest that the decline in Pakistani production is inversely proportional to the rise of Afghani production, and that rather than anti-narcotics activity, the decline in Pakistan is due more to changed market forces.[citation needed]

Conviction for trafficking in heroin carries the death penalty in most Southeast Asia and some East Asia, southern Asia and Middle East countries (see Use of death penalty worldwide for details), among which Malaysia, Singapore and Thailand are the most strict. The penalty applies even to citizens of countries where the penalty is not in place, sometimes causing controversy when foreign visitors are arrested for trafficking, for example the arrest of nine Australians in Bali or the hanging of Australian citizen Van Tuong Nguyen in Singapore, both in 2005.

Risks
Overdose, possibly causing death For intravenous users 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 from this drug injection, as well as the risk of contracting bacterial or fungal endocarditis and possibly Venous sclerosis Poisoning from contaminants added to "cut" or dilute heroin Chronic constipation Tolerance leading to larger doses to achieve the same effect Heroin-induced leukoencephalopathy (Very Rare, Smokers Only) Many countries and local governments have begun funding programs to supply sterile needles to people who inject illegal drugs, in an attempt to reduce some of these contingent risks including 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 injection drug use. But despite the immediate public health benefit of needle exchanges, some see such programs as tacit acceptance of illicit drug use. The United States does not support needle exchanges federally by law, and although some state and local governments do support needle exchange programs, they continue to face harassment by police in most areas. Needle exchanges have been instrumental in arresting the spread of HIV/AIDS in many communities with a significant heroin using population[citation needed], Australia being a leader due to its early inception of needle exchanges. Needle exchange programs have also been attributed for saving the public significant amounts of tax dollars by preventing medical costs which would have been required otherwise for the treatment of diseases spread through the practice of sharing/re-using needles.

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 intravenously. 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.

Depending on drug interactions and numerous other factors, death from overdose can take anywhere from several seconds to several hours. An overdose is immediately reversible with an opioid antagonist injection. Heroin overdoses can occur due to an unexpected increase in the dose or purity or due to diminished opiate tolerance. However, many fatalities reported as overdoses are probably caused by interactions with other depressant drugs like alcohol or benzodiazepines.[6]

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.

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.[citation needed]

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.[citation needed]

A small percentage of heroin smokers may develop symptoms of leukoencephalopathy. This is believed to be caused by an uncommon adulterant that is only active when heated. Symptoms include slurred speech and difficulty walking. Contrary to popular rumor, aluminum foil probably has nothing to do with the development of leukoencephalopathy in heroin users.Heroin-Induced Leukoencephalopathy.