Illicit heroin is sometimes available in freebase form, dulling the sheen and consistency to a matte-white powder.Because of its lower boiling point, the freebase form of heroin is also smokable. It is prevalent in heroin coming from Afghanistan, which as of 2004 produced roughly 87% of the world supply in illicit raw opium. However, production in Mexico has risen six times from 2007 to 2011, changing that percentage and placing Mexico as the second largest opium producer in the world.
Mexican cartels are also known to produce a third type of illicit heroin, commonly called black tar, which results from a simplified, quicker synthesis procedure and contains a high percentage of morphine derivates other than heroin, such as 6-monoacetylmorphine (6-MAM).
As with other opioids, diacetylmorphine is used as both an analgesic and a recreational drug. Frequent and regular administration is associated with tolerance and physical dependence. Internationally, diacetylmorphine is controlled under Schedules I and IV of the Single Convention on Narcotic Drugs. It is illegal to manufacture, possess, or sell diacetylmorphine without a license in almost every country.
Under the chemical names diamorphine and diacetylmorphine, heroin is a legally prescribed controlled drug in the United Kingdom, and is supplied in tablet or injectable form for the same indications as morphine is, often being preferred over morphine due to its lower side-effect profile. It is also available for prescription to long-term users as a form of opioid replacement therapy in the Netherlands, United Kingdom, Switzerland, Germany, and Denmark, alongside psycho-social care—in the same manner that methadone or buprenorphine are used in the United States or Canada—and a similar programme is being campaigned for by liberal political parties in Norway.
The BBC reported that “Worldwide, the UN estimates that as of 2005, there are more than 50 million regular users of heroin, cocaine and synthetic drugs.” Global users of diacetylmorphine are estimated at between 15 and 21 million people aged 15–64.
Under the chemical name diamorphine, diacetylmorphine is prescribed as a strong analgesic in the United Kingdom, where it is given via subcutaneous, intramuscular, intrathecal or intravenous route. Its use includes treatment for acute pain, such as in severe physical trauma, myocardial infarction, post-surgical pain, and chronic pain, including end-stage cancer and other terminal illnesses. In other countries it is more common to use morphine or other strong opioids in these situations. In 2004, the National Institute for Health and Clinical Excellence produced guidance on the management of caesarian section, which recommended the use of intrathecal or epidural diacetylmorphine for post-operative pain relief.
In 2005, there was a shortage of diacetylmorphine in the UK, because of a problem at the main UK manufacturers. Because of this, many hospitals changed to using morphine instead of diacetylmorphine. Although there is no longer a problem with the manufacturing of diacetylmorphine in the UK, some hospitals there have continued to use morphine. The majority, however, continue to use diacetylmorphine, and diacetylmorphine tablets are supplied for pain management.
Diacetylmorphine continues to be widely used in palliative care in the United Kingdom, where it is commonly given by the subcutaneous route, often via a syringe driver, if patients cannot easily swallow oral morphine solution. The advantage of diacetylmorphine over morphine is that diacetylmorphine is more fat soluble and therefore more potent (by injection only), so smaller doses of it are needed for the same analgesic effect. Both of these factors are advantageous if giving high doses of opioids via the subcutaneous route, which is often necessary in palliative care.
The medical use of diacetylmorphine (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 and as such is subject to guidelines surrounding its storage, administration and destruction. Possession of Diamorphine without a prescription is an arrestable offence. When Diamorphine is prescribed in a hospital or similar environment, its administration must be supervised by 2 people who must then complete and sign a CD register detailing the patients name, amount, time, date and route of administration. In the case of a doctor administering diamorphine, then he/she may administer the drug alone, however the rule requiring two registered practitioners (ie. a nurse, midwife or another doctor) to sign the CD register still applies. The use of a “witness” when administering Diamorphine is to avoid the possibility of the drug being diverted onto the black market.
For safety reasons, many UK National Health Service hospitals now only permit the administration of intravenous diamorphine in designated areas. In practice this usually means a critical care unit, an accident and emergency department, operating theatres by an anaesthetist or nurse anaesthetist or other such areas where close monitoring and support from senior staff is immediately available. However, administration by other routes is permitted in other areas of the hospital. This includes subcutaneous, intramuscular, intravenously as part of a patient controlled analgesia setup, and as an already established epidural infusion pump. Subcutaneous infusion, along with subcutaneous and intramuscular ‘bolus’ administration is often used in the patient’s own home, in order to treat severe pain in terminal illness.
Diacetylmorphine is also used as a maintenance drug to treat certain groups of addicts, normally long term chronic IV heroin users, and even in these situations it is only prescribed following exhaustive efforts at treatment via other means. It is thought that heroin users can walk into a clinic and walk out with a prescription but the process takes many weeks before a prescription for Diacetylmorphine is issued. 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, almost always still called by its original trade name of heroin in non-medical settings, is used as a recreational drug for the transcendent relaxation and intense euphoria it induces. Anthropologist Michael Agar once described heroin as “the perfect whatever drug.” Tolerance develops quickly, and users need more of the drug to achieve the same effects. Its popularity with recreational drug users, compared to morphine, reportedly stems from its perceived different effects. In particular, users report an intense rush, an acute transcendent state of euphoria, which occurs while diacetylmorphine is being metabolized into 6-monoacetylmorphine (6-MAM) and morphine in the brain. Some believe that heroin produces more euphoria than other opioids upon injection; one possible explanation is the presence of 6-monoacetylmorphine, a metabolite unique to heroin – although a more likely explanation is the rapidity of onset. While other opioids of recreational use 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 heroin 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 heroin and morphine. When compared to the opioids hydromorphone, fentanyl, oxycodone, and pethidine/meperidine, former addicts showed a strong preference for heroin and morphine, suggesting that heroin and morphine are particularly susceptible to abuse and addiction. Morphine and heroin were also much more likely to produce euphoria and other positive subjective effects when compared to these other opioids.
Some researchers have attempted to explain heroin use and the culture that surrounds it through the use of sociological theories. In Righteous Dopefiend, Philippe Bourgois and Jeff Schonberg use anomie theory to explain why people begin using heroin. By analyzing a community in San Francisco, they demonstrated that heroin use was caused in part by internal and external factors such as violent homes and parental neglect. This lack of emotional, social, and financial support causes strain and influences individuals to engage in deviant acts, including heroin usage. They further found that heroin users practiced “retreatism”, a behavior first described by Howard Abadinsky, in which those suffering from such strain reject society’s goals and institutionalized means of achieving them.
Prescription for Addicts
The UK Department of Health’s Rolleston Committee Report in 1926 established the British approach to diacetylmorphine prescription to users, which was maintained for the next 40 years: dealers were prosecuted, but doctors could prescribe diacetylmorphine to users when withdrawing from it would cause harm or severe distress to the patient. This “policing and prescribing” policy effectively controlled the perceived diacetylmorphine problem in the UK until 1959 when the number of diacetylmorphine addicts doubled every 16 months during a period of ten years, 1959–1968. In 1964 the Brain Committee recommended that only selected approved doctors working at approved specialised centres be allowed to prescribe diacetylmorphine and benzoylmethylecgonine (cocaine) to users. The law was made more restrictive in 1968. Beginning in the 1970s, the emphasis shifted to abstinence and the use of methadone; until now only a small number of users in the UK are prescribed diacetylmorphine.
In 1994, Switzerland began a trial diamorphine maintenance program for users that had failed multiple withdrawal programs. The aim of this program was to maintain the health of the user by avoiding medical problems stemming from the illicit use of diacetylmorphine. The first trial in 1994 involved 340 users, although enrollment was later expanded to 1000 based on the apparent success of the program.
The trials proved diamorphine maintenance to be superior to other forms of treatment in improving the social and health situation for this group of patients. It has also been shown to save money, despite high treatment expenses, as it significantly reduces costs incurred by trials, incarceration, health interventions and delinquency.
Patients appear twice daily at a treatment center, where they inject their dose of diamorphine under the supervision of medical staff. They are required to contribute about 450 swiss franc per month to the treatment costs. A national referendum in November 2008 showed 68% of voters supported the plan, introducing diacetylmorphine prescription into federal law. The trials before were based on time-limited executive ordinances.
The success of the Swiss trials led German, Dutch, and Canadian cities to try out their own diamorphine prescription programs. Some Australian cities (such as Sydney) have instituted legal diacetylmorphine supervised injecting centers, in line with other wider harm minimization programs.
Since January 2009, Denmark has prescribed diamorphine to a few addicts that have tried methadone and subutex without success. Beginning in February 2010, addicts in Copenhagen and Odense will be eligible to receive free diacetylmorphine. Later in 2010 other cities including Århus and Esbjerg will join the scheme. In total, around 230 addicts will be able to receive free diacetylmorphine. However, Danish addicts will only be able to inject heroin according to the policy set by Danish National Board of Health. Of the estimated 1500 drug users who do not benefit from the current oral substitution treatment, approximately 900 will not be in the target group for treatment with injectable diacetylmorphine, either because of “massive multiple drug abuse of non-opioids” or “not wanting treatment with injectable diacetylmorphine”.
In July 2009, the German Bundestag passed a law allowing diacetylmorphine prescription as a standard treatment for addicts; a large-scale trial of diacetylmorphine prescription had been authorized in that country in 2002.
Detection in Biological Fluids
The major metabolites of diacetylmorphine, 6-MAM, morphine, morphine-3-glucuronide and morphine-6-glucuronide, may be quantitated in blood, plasma or urine to monitor for abuse, confirm a diagnosis of poisoning or assist in a medicolegal death investigation. Most commercial opiate screening tests cross-react appreciably with these metabolites, as well as with other biotransformation products likely to be present following usage of street-grade diacetylmorphine such as 6-acetylcodeine and codeine. However, chromatographic techniques can easily distinguish and measure each of these substances. When interpreting the results of a test, it is important to consider the diacetylmorphine usage history of the individual, since a chronic user can develop tolerance to doses that would incapacitate an opiate-naive individual, and the chronic user often has high baseline values of these metabolites in his system. Furthermore, some testing procedures employ a hydrolysis step prior to quantitation that converts many of the metabolic products to morphine, yielding a result that may be 2 times larger than with a method that examines each product individually.
Like most opioids, unadulterated heroin does not cause many long-term complications other than dependence and constipation. Due to increased vulnerability to infectious agents, particularly viruses and intracellular bacteria resulting from the suppression of various cell-mediated immune pathways, the use of heroin and other opioids, even at normal therapeutic levels, may lead to opportunistic infections, which carry their own lasting effects. The average purity of street heroin in the UK varies between 30% and 50% and heroin that has been seized at the border has purity levels between 40% and 60%; this variation has led to people suffering from overdoses as a result of the heroin missing a stage on its journey from port to end user, as each set of hands that the drug passes through adds further adulterants, the strength of the drug reduces, with the effect that if steps are missed, the purity of the drug reaching the end user is higher than they are used to and because they are unable to tolerate the increase, an overdose ensues. Intravenous use of heroin (and any other substance) with non-sterile needles and syringes or other related equipment may lead to:
- The risk of contracting blood-borne pathogens such as HIV and hepatitis by the sharing of needles
- The risk of contracting bacterial or fungal endocarditis and possibly venous sclerosis
- Poisoning from contaminants added to “cut” or dilute heroin
- Physical dependence can result from prolonged use of all opioids, resulting in withdrawal symptoms on cessation of use
- Decreased kidney function (although it is not currently known if this is because of 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 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.
Anthropologists Philippe Bourgois and Jeff Schonberg, performed a decade of field work among homeless heroin and cocaine addicts in San Francisco, published in 2009. They reported that the African-American addicts they observed were more inclined to “direct deposit” heroin into a vein, while “skin-popping” was a far more widespread practice: “By the midpoint of our fieldwork, most of the whites had given up searching for operable veins and skin-popped. They sank their needles perfunctorily, often through their clothing, into their fatty tissue.”) Bourgois and Schonberg describes how the cultural difference between the African-Americans and the whites leads to this contrasting behavior, and also points out that the two different ways to inject heroin comes with different health risks. Skin-popping more often results in abscesses, and direct injection more often leads to fatal overdose and also to hepatitis C and HIV infection.
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 because of anoxia resulting from the breathing reflex being suppressed by agonism of µ-opioid receptors. An overdose is immediately reversible with an opioid antagonist injection. Diacetylmorphine overdoses can occur because of an unexpected increase in the dose or purity or because of 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 quote the median lethal dose (for an average 75 kg opiate-naive individual) as being between 75 and 375 mg. Illicit 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. Diacetylmorphine 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. 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 is sometimes used in combination with heroin, and is referred to as a speedball when injected or moonrocks when smoked together. Cocaine acts as a stimulant, whereas heroin acts as a depressant. Coadministration provides an intense rush of euphoria with a high that combines both effects of the drugs, while excluding the negative effects, such as anxiety and sedation. The effects of cocaine wear off far more quickly than heroin, thus if an overdose of heroin was used to compensate for cocaine, the end result is fatal respiratory depression.
The withdrawal syndrome from heroin (the so-called “cold turkey”) 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, akathisia, priapism, extra sensitivity of the genitals in females, general feeling of heaviness, excessive yawning or sneezing, tears, rhinorrhea, sleep difficulties (insomnia), cold sweats, chills, severe muscle and bone aches, nausea, vomiting, diarrhea, cramps, watery eyes, fever and cramp-like pains and involuntary spasms in the limbs (thought to be an origin of the term “kicking the habit”).
When taken orally, heroin 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 because of the presence of the acetyl groups, which render it much more fat soluble than morphine itself. Once in the brain, it then is deacetylated variously into the inactive 3-monoacetylmorphine and the active 6-monoacetylmorphine (6-MAM), and then to morphine, which bind to μ-opioid receptors, resulting in the drug’s euphoric, analgesic (pain relief), and anxiolytic (anti-anxiety) effects; heroin itself exhibits relatively low affinity for the μ receptor. Unlike hydromorphone and oxymorphone, however, administered intravenously, heroin 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 that 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 heroin results in a number of physiological changes, including an increase in the production of μ-opioid receptors (upregulation). These physiological alterations lead to tolerance and dependence, so that cessation of heroin use results in a set of remarkably uncomfortable symptoms including pain, anxiety, muscle spasms, and insomnia called the opioid withdrawal syndrome. Depending on usage it has an onset four to 24 hours after the last dose of heroin. Morphine also binds to δ- and κ-opioid receptors.
There is also evidence that 6-MAM binds to a subtype of μ-opioid receptors that are also activated by the morphine metabolite morphine-6β-glucuronide but not morphine itself. The third substype of third opioid type is the mu-3 receptor, which may be a commonality to other six-position monoesters of morphine. The contribution of these receptors to the overall pharmacology of heroin remains unknown.
A subclass of morphine derivatives, namely the 3,6 esters of morphine, with similar effects and uses, includes the clinically used strong analgesics nicomorphine (Vilan), and dipropanoylmorphine; there is also the latter’s dihydromorphine analogue, diacetyldihydromorphine (Paralaudin). Two other 3,6 diesters of morphine invented in 1874-5 along with diacetylmorphine, dibenzoylmorphine and acetylpropionylmorphine, were made as substitutes after it was outlawed in 1925 and, therefore, sold as the first “designer drugs” until they were outlawed by the League of Nations in 1930.
In 1895, the German drug company Bayer marketed diacetylmorphine as an over-the-counter drug under the trademark name Heroin. The name was derived from the Greek word “Heros” because of its perceived “heroic” effects upon a user. It was developed chiefly as a morphine substitute for cough suppressants that did not have morphine’s addictive side-effects. Morphine at the time was a popular recreational drug, and Bayer wished to find a similar but non-addictive substitute to market. However, contrary to Bayer’s advertising as a “non-addictive morphine substitute,” heroin would soon have one of the highest rates of dependence among its users.
The opium poppy was cultivated in lower Mesopotamia as long ago as 3400 BCE. 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 or morphine diacetate. The compound was sent to F. M. Pierce of Owens College in Manchester for analysis. Pierce told Wright:
Doses … were subcutaneously injected into young dogs and rabbits … with the following general results … great prostration, fear, and sleepiness speedily following the administration, the eyes being sensitive, and pupils constrict, considerable salivation being produced in dogs, and slight tendency to vomiting in some cases, but no actual emesis. Respiration was at first quickened, but subsequently reduced, and the heart’s action was diminished, and rendered irregular. Marked want of coordinating power over the muscular movements, and loss of power in the pelvis and hind limbs, together with a diminution of temperature in the rectum of about 4°.
Wright’s invention did not lead to any further developments, and diacetylmorphine became popular only 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 trademark name Heroin as a non-addictive morphine substitute and cough suppressant. Bayer marketed the drug as a cure for morphine addiction before it was discovered that it rapidly metabolizes into morphine. As such, diacetylmorphine is in essence 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 diacetylmorphine 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.
The Health Committee of the League of Nations banned diacetylmorphine in 1925, although it took more than three years for this to be implemented. In the meantime, the first designer drugs, viz. 3,6 diesters and 6 monoesters of morphine and acetylated analogues of closely related drugs like hydromorphone and dihydromorphine were produced in massive quantities to fill the worldwide demand for diacetylmorphine—this continued until 1930 when the Committee banned diacetylmorphine analogues with no therapeutic advantage over drugs already in use, the first major legislation of this type.
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.