Opiate
Encyclopedia
Medicine
Medicine is the science and art of healing. It encompasses a variety of health care practices evolved to maintain and restore health by the prevention and treatment of illness....
, the term opiate describes any of the narcotic
Narcotic
The term narcotic originally referred medically to any psychoactive compound with any sleep-inducing properties. In the United States of America it has since become associated with opioids, commonly morphine and heroin and their derivatives, such as hydrocodone. The term is, today, imprecisely...
opioid alkaloid
Alkaloid
Alkaloids are a group of naturally occurring chemical compounds that contain mostly basic nitrogen atoms. This group also includes some related compounds with neutral and even weakly acidic properties. Also some synthetic compounds of similar structure are attributed to alkaloids...
s found as natural products in the opium poppy
Opium poppy
Opium poppy, Papaver somniferum, is the species of plant from which opium and poppy seeds are extracted. Opium is the source of many opiates, including morphine , thebaine, codeine, papaverine, and noscapine...
plant.
Overview
Opiates are so named because they are constituents or derivatives of constituents found in opiumOpium
Opium is the dried latex obtained from the opium poppy . Opium contains up to 12% morphine, an alkaloid, which is frequently processed chemically to produce heroin for the illegal drug trade. The latex also includes codeine and non-narcotic alkaloids such as papaverine, thebaine and noscapine...
, which is processed from the latex
Latex
Latex is the stable dispersion of polymer microparticles in an aqueous medium. Latexes may be natural or synthetic.Latex as found in nature is a milky fluid found in 10% of all flowering plants . It is a complex emulsion consisting of proteins, alkaloids, starches, sugars, oils, tannins, resins,...
sap of the opium poppy, Papaver somniferum. The major biologically active opiates found in opium are morphine
Morphine
Morphine is a potent opiate analgesic medication and is considered to be the prototypical opioid. It was first isolated in 1804 by Friedrich Sertürner, first distributed by same in 1817, and first commercially sold by Merck in 1827, which at the time was a single small chemists' shop. It was more...
, codeine
Codeine
Codeine or 3-methylmorphine is an opiate used for its analgesic, antitussive, and antidiarrheal properties...
, papaverine
Papaverine
Papaverine is an opium alkaloid antispasmodic drug, used primarily in the treatment of visceral spasm, vasospasm , and occasionally in the treatment of erectile dysfunction...
and to a lesser extent thebaine
Thebaine
Thebaine , its name coming from the Greek Θῆβαι, Thēbai, an ancient city in Upper Egypt, is an opiate alkaloid. A minor constituent of opium, thebaine is chemically similar to both morphine and codeine, but has stimulatory rather than depressant effects, causing convulsions similar to strychnine...
, which is not narcotic. Semi-synthetic opioids such as hydromorphone
Hydromorphone
Hydromorphone, a more common synonym for dihydromorphinone, commonly a hydrochloride is a very potent centrally-acting analgesic drug of the opioid class. It is a derivative of morphine, to be specific, a hydrogenated ketone thereof and, therefore, a semi-synthetic drug...
, oxycodone
Oxycodone
Oxycodone is an opioid analgesic medication synthesized from opium-derived thebaine. It was developed in 1916 in Germany, as one of several new semi-synthetic opioids in an attempt to improve on the existing opioids: morphine, diacetylmorphine , and codeine.Oxycodone oral medications are generally...
, and hydrocodone
Hydrocodone
Hydrocodone or dihydrocodeinone is a semi-synthetic opioid derived from either of two naturally occurring opiates: codeine and thebaine. It is an orally active narcotic analgesic and antitussive...
are derived from these substances, especially morphine, codeine, and thebaine. Noscapine
Noscapine
Noscapine is a benzylisoquinoline alkaloid from plants of the Papaveraceae family, without significant painkilling properties. This agent is primarily used for its antitussive effects. It has also been shown to have anticancer activity...
, along with approximately 25 other alkaloids, are also present in opium, but have little to no effect on the human central nervous system
Central nervous system
The central nervous system is the part of the nervous system that integrates the information that it receives from, and coordinates the activity of, all parts of the bodies of bilaterian animals—that is, all multicellular animals except sponges and radially symmetric animals such as jellyfish...
, and are not usually considered to be opiates.
Opiates belong to the large biosynthetic group of benzylisoquinoline
Benzylisoquinoline
1-Benzylisoquinoline is a chemical compound, and the structural backbone of many alkaloids with a wide variety of structures, including papaverine, noscapine, codeine, morphine, apomorphine, berberine, protopine and tubocurarine.-Biosynthesis:...
alkaloids.
The full synthesis of opiates from naphthoquinone
Naphthoquinone
Naphthoquinone is a class of natural phenols based on the C6-C4 skeleton.1,4-Naphthoquinone can be viewed as derivatives of naphthalene through the replacement of two hydrogen atoms by two ketone groups....
(Gates synthesis) or from other simple organic starting materials is tedious and not economical. Thus, most of the opiate-type analgesics in use today are extracted from Papaver somniferum or semi-synthesized from thebaine
Thebaine
Thebaine , its name coming from the Greek Θῆβαι, Thēbai, an ancient city in Upper Egypt, is an opiate alkaloid. A minor constituent of opium, thebaine is chemically similar to both morphine and codeine, but has stimulatory rather than depressant effects, causing convulsions similar to strychnine...
.
Terminology
In the traditional sense, opiate has referred to only the alkaloids in opium and the natural and semi-synthetic derivatives of opiumOpium
Opium is the dried latex obtained from the opium poppy . Opium contains up to 12% morphine, an alkaloid, which is frequently processed chemically to produce heroin for the illegal drug trade. The latex also includes codeine and non-narcotic alkaloids such as papaverine, thebaine and noscapine...
. The term is often incorrectly used to refer to all drugs with opium- or morphine-like pharmacological
Pharmacology
Pharmacology is the branch of medicine and biology concerned with the study of drug action. More specifically, it is the study of the interactions that occur between a living organism and chemicals that affect normal or abnormal biochemical function...
action, which are more properly classified under the broader terms opioid
Opioid
An opioid is a psychoactive chemical that works by binding to opioid receptors, which are found principally in the central and peripheral nervous system and the gastrointestinal tract...
.
Morphine
Morphine is by far the most prevalent alkaloidAlkaloid
Alkaloids are a group of naturally occurring chemical compounds that contain mostly basic nitrogen atoms. This group also includes some related compounds with neutral and even weakly acidic properties. Also some synthetic compounds of similar structure are attributed to alkaloids...
in opium, making up anywhere from 10% to 16% of the total mass, and is responsible for many of its potentially harmful effects, such as pulmonary edema, respiratory depression, coma, cardiac and/or respiratory failure, with a normal lethal dose of 120 to 250 mg which corresponds to approximately two grams of opium. However, the occurrence of pulmonary edema is uncommon. The most frequently-reported occurrences of opiate-induced pulmonary edema are among recreational heroin users. Although uncommon, reports of morphine-induced pulmonary edema are not unheard of. The primary difference is the more careful supervision of morphine administration compared to the lack of supervision and medical expertise among illicit heroin users. On the other hand, morphine may also be used in the treatment of pulmonary edema. Despite morphine's being the most medically-significant alkaloid, larger quantities of the milder codeine—most of it manufactured from morphine—are consumed medically, as codeine has a greater and more predictable oral bioavailability than morphine, making it easier to titrate one's dose.
The quantity of morphine produced by poppy plants in the form of opium depends on two factors: the percentage of morphine in the opium, and the quantity of opium produced. The latter factor, in turn, depends in part on whether each capsule is bled several times, or just once. In Turkey
Turkey
Turkey , known officially as the Republic of Turkey , is a Eurasian country located in Western Asia and in East Thrace in Southeastern Europe...
, Bulgaria
Bulgaria
Bulgaria , officially the Republic of Bulgaria , is a parliamentary democracy within a unitary constitutional republic in Southeast Europe. The country borders Romania to the north, Serbia and Macedonia to the west, Greece and Turkey to the south, as well as the Black Sea to the east...
, Greece
Greece
Greece , officially the Hellenic Republic , and historically Hellas or the Republic of Greece in English, is a country in southeastern Europe....
, and the Balkans
Balkans
The Balkans is a geopolitical and cultural region of southeastern Europe...
, each capsule is bled only once, but, in most other opium-producing countries, like Iran
Iran
Iran , officially the Islamic Republic of Iran , is a country in Southern and Western Asia. The name "Iran" has been in use natively since the Sassanian era and came into use internationally in 1935, before which the country was known to the Western world as Persia...
, India
India
India , officially the Republic of India , is a country in South Asia. It is the seventh-largest country by geographical area, the second-most populous country with over 1.2 billion people, and the most populous democracy in the world...
and Afghanistan
Afghanistan
Afghanistan , officially the Islamic Republic of Afghanistan, is a landlocked country located in the centre of Asia, forming South Asia, Central Asia and the Middle East. With a population of about 29 million, it has an area of , making it the 42nd most populous and 41st largest nation in the world...
, the capsules are incised repeatedly, often four or five times on different days, until they will yield no more latex. The quantity of latex falls off rapidly with later incisions, and so does the morphine content. Usually, all the opium obtained is mixed together. This is probably the chief reason for the often lower morphine content of Iranian and Indian opiums as compared with Turkish and Balkan opiums, although it must also be recognized that there are low-yielding and high-yielding strains of the poppy, one or the other of which may predominate in a given region.
Samples of opium assaying some 15% morphine from Japan
Japan
Japan is an island nation in East Asia. Located in the Pacific Ocean, it lies to the east of the Sea of Japan, China, North Korea, South Korea and Russia, stretching from the Sea of Okhotsk in the north to the East China Sea and Taiwan in the south...
, Indochina
Indochina
The Indochinese peninsula, is a region in Southeast Asia. It lies roughly southwest of China, and east of India. The name has its origins in the French, Indochine, as a combination of the names of "China" and "India", and was adopted when French colonizers in Vietnam began expanding their territory...
, and Afghanistan, as well as from Turkey, Greece, and the Balkans have been examined by the United Nations Secretariat. Afghanistan
Opium production in Afghanistan
Afghanistan has been the greatest illicit opium producer in the entire world, ahead of Burma and the "Golden Triangle" since 1992, excluding the year 2001. Afghanistan is the main producer of opium in the "Golden Crescent". Opium production in Afghanistan has been on the rise since U.S....
at one time exported two grades of opium, one of about 15% morphine and the other about 10%. The morphine content of dry capsule-chaff is about 0.25% to 0.5%, when not washed out by rain. Here again there are low-yielding and high-yielding varieties, but proper agricultural selection of poppies for morphine production means taking into account not only the percentage yield of morphine, but also the total weight of capsule-chaff produced per hectare, the poppy seed production per hectare, and other factors.
Most of the licit morphine is used to manufacture codeine
Codeine
Codeine or 3-methylmorphine is an opiate used for its analgesic, antitussive, and antidiarrheal properties...
through O-methylation
Methylation
In the chemical sciences, methylation denotes the addition of a methyl group to a substrate or the substitution of an atom or group by a methyl group. Methylation is a form of alkylation with, to be specific, a methyl group, rather than a larger carbon chain, replacing a hydrogen atom...
. Morphine is also used to manufacture other drugs, such as heroin, dihydromorphine
Dihydromorphine
Dihydromorphine is a semi-synthetic opioid invented in Germany in 1900. In structure, it is very similar to morphine, the only difference being the reduction of the double bond between positions 7 and 8 in morphine to a single bond...
, hydromorphone
Hydromorphone
Hydromorphone, a more common synonym for dihydromorphinone, commonly a hydrochloride is a very potent centrally-acting analgesic drug of the opioid class. It is a derivative of morphine, to be specific, a hydrogenated ketone thereof and, therefore, a semi-synthetic drug...
, and many others. Of these, the conversion of morphine to heroin is particularly noteworthy due to heroin's unusual pharmacological properties. The acetylation of morphine's two hydroxyl groups results in a different drug in chemical structure, but nearly identical with regard to pharmacological properties, the principal difference being lipid solubility. This increase in lipid solubility allows heroin to enter the brain more rapidly than morphine.
As heroin is not pharmacologically active it must first be metabolized. The active metabolites of heroin are morphine, 6-monoacetylmorphine and 3-monoacetylmorphine.
Codeine
The highest percentages of codeine obtained by the United Nations Secretariat (averaging about 4.3%) were found in opium samples that came from north-eastern Asia (Korea, northern China).
The manufacturers’ statistics do not ordinarily show all the codeine obtained from opium. Some of it co-precipitates with the morphine, and there is no necessity of purifying the morphine completely of its codeine content, especially if it is to be used to manufacture more codeine.
Codeine is used to manufacture dihydrocodeine
Dihydrocodeine
Dihydrocodeine, also called DHC, Drocode, Paracodeine and Parzone and known by the brand names of Synalgos DC, Panlor DC, Panlor SS, Contugesic, New Bron Solution-ACE, Huscode, Drocode, Paracodin, Codidol, Didor Continus, Dicogesic, Codhydrine, Dekacodin, DH-Codeine,...
, hydrocodone
Hydrocodone
Hydrocodone or dihydrocodeinone is a semi-synthetic opioid derived from either of two naturally occurring opiates: codeine and thebaine. It is an orally active narcotic analgesic and antitussive...
, and others. It may also be used to manufacture the drugs ordinarily made by conversion of thebaine.http://www.poppies.org/news/99502043380992.shtml#n01
Thebaine and papaverine
Indochina
The Indochinese peninsula, is a region in Southeast Asia. It lies roughly southwest of China, and east of India. The name has its origins in the French, Indochine, as a combination of the names of "China" and "India", and was adopted when French colonizers in Vietnam began expanding their territory...
, which at the same time had virtually no papaverine. Both thebaine and papaverine have been high in most Iranian samples run. Papaverine is low in some Afghan and Indian opiums.
Opium
Opium is the dried latex obtained from the opium poppy . Opium contains up to 12% morphine, an alkaloid, which is frequently processed chemically to produce heroin for the illegal drug trade. The latex also includes codeine and non-narcotic alkaloids such as papaverine, thebaine and noscapine...
. However, it is converted into several other narcotics that have medical use: hydrocodone
Hydrocodone
Hydrocodone or dihydrocodeinone is a semi-synthetic opioid derived from either of two naturally occurring opiates: codeine and thebaine. It is an orally active narcotic analgesic and antitussive...
, acetyldihydrocodeine
Acetyldihydrocodeine
Acetyldihydrocodeine is an opiate derivative discovered in Germany in 1914 and was used as as a cough suppressant and analgesic. It is not commonly used, but has activity similar to other opiates...
, oxycodone
Oxycodone
Oxycodone is an opioid analgesic medication synthesized from opium-derived thebaine. It was developed in 1916 in Germany, as one of several new semi-synthetic opioids in an attempt to improve on the existing opioids: morphine, diacetylmorphine , and codeine.Oxycodone oral medications are generally...
, and the highly-potent and powerful narcotic oxymorphone
Oxymorphone
Oxymorphone or 14-Hydroxydihydromorphinone is a powerful semi-synthetic opioid analgesic first developed in Germany circa 1914, patented in the USA by Endo Pharmaceuticals in 1955 and introduced to the United States market in January 1959 and other countries around the same time...
, are all used medically to control pain and for other effects on the central nervous system. Buprenorphine
Buprenorphine
Buprenorphine is a semi-synthetic opioid that is used...
is also synthesized from it, and is most typically used medically to treat opioid withdrawal.
Papaverine, conversely, is very useful medically for its antispasmodic effects, so much so that supplies available from opium have sometimes run short. It is then manufactured synthetically.http://www.poppies.org/news/99502043380992.shtml#n01
Withdrawal effects
Opiate withdrawal syndrome effects are associated with cessation of prolonged opiate usage.In facilities the logical threat of relapse is possible when Post-acute-withdrawal syndrome is under-emphasized to patients in transitional phases, especially with short-term suboxone, methadone
Methadone
Methadone is a synthetic opioid, used medically as an analgesic and a maintenance anti-addictive for use in patients with opioid dependency. It was developed in Germany in 1937...
or health
Health care
Health care is the diagnosis, treatment, and prevention of disease, illness, injury, and other physical and mental impairments in humans. Health care is delivered by practitioners in medicine, chiropractic, dentistry, nursing, pharmacy, allied health, and other care providers...
facilities.