III. THEBAINE AND PAPAVERINE
Pages: 13 to 14
Creation Date: 1953/01/01
The six opium alkaloids which occur naturally in the largest amounts are morphine, narcotine, codeine, thebaine, papaverine and narceine. Of these, three are phenanthrene alkaloids and are under international control: these are morphine, codeine, and thebaine. They are all three used in the drug industry, thebaine usually for conversion into some derivative which is more useful medically. Of the other three, not under international control, narcotine and narceine have scarcely any medical or other uses. Consequently, the four economically significant alkaloids of opium are morphine, codeine, thebaine and papaverine.
About twenty other alkaloids exist in opium but they have little or no significance medically or economically up to the present time. A number of other "opium alkaloids" are commercial products and are used medically, but·they are not obtained directly from opium, but by conversion of morphine, codeine and thebaine.
The alkaloids of the poppy plant are the same as those of opium. The relative proportions of the different alkaloids vary greatly, however, in different kinds of opium and certainly also in different varieties of the poppy. All varieties, however, belong to one species of poppy, Papaver somniferum.
Morphine is the chief alkaloid of opium both in amount and in medical importance, although larger, quantities of the milder codeine - most of it manufactured from morphine - are consumed medically
The expression of the morphine content of opium as a percentage depends in part on the moisture content. When the government purchases the opium as soon as practicable after it is collected, the moisture content is then usually about 30 per cent. Commercial opium usually has around 15 to 10 per cent moisture. Opium apparently dry at ordinary temperatures still retains considerable moisture - usually about 6 per cent - which can be driven off at about 103 degrees centigrade.
A normal, unadulterated opium of any type, in the air-dry condition, usually has between 8 and 19 per cent of morphine. The principal commercial opiums generally have approximately the following morphine contents: Yugoslavia 15 per cent; Turkey 13 per cent; Iran 11 per cent; India 11 per cent.
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, oronce only. In Turkey, Yugoslavia, Greece and Bulgaria, it is customary to bleed each capsule only once, but in most other opium-producing countries 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, as was shown by Annett1 in India. Usually, all the opium so obtained is mixed together. This is probably the chief reason for the lower morphine content of Iranian and Indian opiums as compared with Turkish and Yugoslav 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 district.
Samples of opium assaying some 15 per cent morphine from Japan, Indochina and Afghanistan, as well as from Turkey, Greece and Yugoslavia have been examined by the Secretariat. Afghanistan at one time exported two grades of opium, one of about 15 per cent morphine and the other about 10 per cent.
The morphine content of dry capsule-chaff is about 0.25 per cent to 0.5 per cent, 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.
Morphine is used to manufacture apomorphine (not subject to the conventions), codeine, ethyl-morphine, beta-4-morpholinylethylmorphine, benzylmorphine, diacetylmorphine, dihydromorphine, hydromorphone (dihydromorphinone), metopon, morphine-N-oxide, desomorphine (dihydrodesoxy-morphine) and N-allyl-normorphine.
The codeine content of opium is related inversely to the morphine content but only in a general way.
1Annett, Harold Edward, "Factors Influencing Alkaloidal Content and Yield of Latex in the Opium Poppy ( Papaver somniferum)." Biochemical Journal, 14, 618-36 (1920).
The codeine content is closely related to the type of opium produced in a given district or even in some cases in an entire country. The opiums of the principal exporting countries have approximately the following percentages of codeine: Yugoslavia 1.25 per cent; Turkey 1.25 per cent; Iran 3.4 per cent; India 3.0 per cent.
The highest percentages of codeine obtained by the Secretariat (averaging about 4.3 per cent) were found in opium samples which 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 and acetyldihydrocodeine, and may also be used to manufacture the drugs ordinarily made by conversion of thebaine.
The Secretariat is currently engaged in a survey, the most extensive ever attempted in this field, of opium samples from different regions for their thebaine and papaverine percentages. As yet, it is premature for general conclusions. However, the highest thebaine percentages found (nearly 5 per cent) were in some samples from Indochina, 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.
Thebaine is the most poisonous opium alkaloid and is scarcely used medically. It is even omitted from some of the preparations of mixed opium alkaloids which are used as soluble substitutes for opium. However, it is converted into several other narcotics which have medical use: hydrocodone (dihydrocodeinone), acetyldihydrocodeinone and oxycodone (dihydrohydroxycodeinone).
Papaverine has a considerable medical use, so much so that supplies available from opium have sometimes run short. It is then manufactured synthetically.