Opium (U. S. P.)—Opium.

Preparations: Vinegar of Opium - Confection of Opium - Opium Plaster - Extract of Opium - Liquid Extract of Opium - Liniment of Opium - Pills of Opium - Pills of Opium and Lead - Compound Powder of Opium. - Syrup of Poppy - Tincture of Opium - Tincture of Deodorized Opium - Camphorated Tincture of Opium - Troches of Glycyrrhiza and Opium - Wine of Opium - Compound Tincture of Serpentaria
Related preparations: Compound Powder of Morphine - Tincture of Chloroform and Morphine - Syrup of Morphine Sulphate - Catarrh Powder - Morphine Lozenges - Troches of Morphine and Ipecac - Compound Troches of Liquorice
Related entries: Rhoeados Petala.—Red-Poppy Petals - Papaveris Capsulae.—Poppy Capsules

The concrete, milky exudation obtained by incising the unripe capsules of Papaver somniferum, Linné (Nat. Ord.—Papaveraceae), and yielding, in its normal, moist condition, not less than nine (9) per cent of crystallized morphine, when assayed by the process given below U. S. P.). (For botanical description of poppy, see Papaveris Capsulae.)
SYNONYMS: Meconium, Succus thebaicus.

Official Forms of Opium.—I. OPIUM (as above indicated). II. OPII PULVIS, Powdered opium. III. OPIUM DEODORATUM, Opium denarcotisatum, Deodorized opium, Denarcotized opium.

History, Commercial Sources, and Description.—Opium was known to the ancient Greeks, being mentioned in the writings of Theophrastus (about 370 to 286 B. C.), and by the writers of the first century, e. g., Dioscorides and Pliny. Its most probable geographical source was then Asia Minor. Egyptian (Thebaïc) opium is recorded as early as the sixth century. The knowledge of the drug was spread eastward by the Arabs. During the middle ages it was used in Europe only as a medicine, and entered into most of the narcotic preparations known as theriac. In eastern Asia, however, its use as a stimulant gradually increased and received a powerful impetus since about 1770, by the exportations of opium from India into China. This trade has fallen off considerably, owing to extensive production of the drug by the Chinese themselves. The most notable event in the chemical history of the drug was the discovery of the first alkaloid known, morphine, by Sertürner, in 1811.

The opium met with in commerce is principally that from Asia Minor, which was the kind expressly demanded by the U. S. P., 1880, and the Br. Pharm., 1885, and which is still required by the Ger. Pharm., 1890. The present U. S. P. and British Pharmacopoeia do not specify the origin of opium; still, most of the opium entering this country, comes from Asia Minor. Other opium-producing countries are Persia, India, Egypt, China, Australia, and some parts of Europe.

ASIA MINOR OPIUM, Turkey opium, Smyrna opium, Constantinople opium.—This is obtained from Papaver somniferum, Linné, var. glabrum, Boissier. In the northwestern provinces of Asia Minor, opium cultivation is in the hands of small holders of land, owing to the scarcity of hired labor. The poppy requires a naturally moist and rich soil, much manure, and diligent hoeing and weeding, which is done mostly by women and children, yet the opium crop is very uncertain, because the poppy may be injured or destroyed by spring frosts, drought or locusts. About the end of May the plants begin to ripen, and a few days after the petals have fallen, the head or capsule is ready for incision. This is done on hot afternoons in order that the exuding juice may dry rapidly. A transverse cut is made with a knife in the lower part of the capsule, the incision being carried round to near its starting point. Great care must be taken not to cut too deep, i. e., to avoid penetrating the interior wall of the seed-vessel, because in this case the juice would flow into the inside and be lost. The following morning, the capsules are scraped off with a blunt instrument and the dried juice placed on a leaf. Night-dew promotes the flow of juice and increases the yield, but the opium is darker than when the night is dry. A high wind is also harmful, because of the dust it throws on the opium. A crop of 5 to 8 ⅓ pounds of opium, and 200 pounds of poppy-seed, from 1 toloom of land (1600 square yards), is considered a good yield; in some years only a little over ½ pound has been obtained. After the opium is collected, the seeds are shaken out, expressed in hand presses, and the oil thus obtained is used for burning and for eating purposes. Part of the poppy-seeds are sold to Smyrna merchants who find a market for them in Europe. The opium, before it is marketed, is wrapped in poppy leaves, and dried in the shade, and then put into thin cotton bags which are sealed and placed into round baskets. These are sent to Smyrna, carried by mules, each animal carrying two baskets, weighing from 130 to 162 pounds each. Most of these baskets also contain about 5 per cent of inferior grades, partly adulterated with sand, pounded poppy-heads, half-dried apricots, dried grape-juice mixed with flour and sometimes turpentine, figs, or gum tragacanth. The bags are opened in Smyrna, examined by a government official, and the lowest grades (chicantee, chikinti) are rejected and sold at cheaper rates to manufacturers of morphine. Upon repacking, the seeds of some Rumex species are strewn between the opium cakes, in order to prevent their agglutinating together. Mr. Sidney H. Maltass, who gives the foregoing information (Pharm. Jour. Trans., Vol. XIV, 1855, pp. 395-400), also states that the distinction usually made between Constantinople and Smyrna opium does not really exist, as the opium from the intermediate districts may be sent to both places. At the time of his report, preference was given to Smyrna, because the opportunities for smuggling were greater in the latter place. (For additional information on Smyrna opium, see an excellent article by E. R. Heffter, Amer. Jour. Pharm., 1868, p. 362, and translation of an official Turkish bulletin oil poppy-growing, Amer. Jour. Pharm., 1883, p. 413, from Pharm. Jour. Trans.)

Good commercial opium is described by the U. S. P. as occurring "in irregular or subglobular cakes, with the remnants of poppy leaves and fruits of a species of Rumex adhering to the surface; plastic, or of a harder consistence; chestnut-brown or darker, and somewhat shining; internally showing some tears and fragments of vegetable tissue. It has a sharp, narcotic odor, and a peculiar, bitter taste"—(U. S. P.). The Smyrna opium cakes vary in weight from about 300 to 700 grammes, or about ½ to 2 pounds; in rare cases, they weigh as much as 3 kilogrammes, or over 6 pounds (Flückiger, Pharmacognosie, 3d ed., 1891, p. 178). The only change that good opium undergoes by keeping, is that of becoming gradually hard; too moist varieties are apt to become moldy.

PERSIAN OPIUM.—This variety first appeared on the market in the later fifties. It is chiefly grown in the provinces of Kermanshah and Ispahan, from the variety Papaver somniferum, Linné, var. album (Papaver officinale, Gmelin), and is said to contain, when pure, from 13 to 16 per cent of morphine, while the Smyrna opium contains, at best, little over 13.5 per cent (Amer. Jour. Pharm., 1885, p. 36). Persian opium, however, has greatly lost in favor, owing to its being frequently adulterated. It is mixed, for example, with evaporated grape must, or linseed oil (8 to 10 per cent), probably in order to facilitate its being rolled into small balls or cylinders. W. Stoeder (Jahresb. der Pharm., 1884, p. 335) found the best variety to contain about 12 per cent of morphine. It occurs in commerce in the form of cones, weighing about 180 to 300 grammes, or in brick shape, or in circular, flat cakes of 600 grammes weight, or in the form of small cylinders wrapped in glazed paper, and weighing about 15 grammes (see Reveil, Pharm. Jour. Trans., Vol. II, 1860, p. 271). It is shipped from the Persian ports Bushahr and Bender Abbas, and now and then reaches the London market, it being used chiefly in the preparation of pure morphine.

EAST INDIA OPIUM.—About 1770 the Calcutta authorities embarked upon the cultivation of opium and its exportation into China, in order to raise revenue for the benefit of the government officials. The astonishing financial success of this measure, however, induced the East Indian Company to assume entire control of this trade, and to exercise strict supervision over the production and disposition of opium (see K. von Scherzer, Fach. Berichte ü. d. Oest. Ung. Exp. n. Siam, China and Japan, 1872). For the last 30 years, this trade has been gradually falling off, owing to the competition of the Chinese products (see Pharm. Jour. Trans., Vol. III, 1896, p. 465).

Although East India opium is raised in greater quantity than any other kind of opium, probably, except the Chinese, it reaches the western markets only in small quantities. The principal varieties are the Bengal and Malwah opiums. The Bengal opium is raised in the Central Ganges territory between Patna and Benares, and is fully controlled by the government. The opium growers must obtain a license, and must sell their product, which must possess a specified consistency (70 per cent of dry substance), to the government. It is produced in nearly the same manner and under the same precautions as Smyrna opium. The capsules are repeatedly cut by means of a knife with several parallel blades tied together. The opium growers bring their product to the government factories where it is roughly assayed, mixed in vats and filled into previously prepared shells of agglutinated poppy leaves. The balls thus formed weigh about 2 kilogrammes each; they are then rolled in "poppy-trash," i. e., broken leaves, capsules, and stalks, then dried by exposure to the air and in drying rooms, and finally put in chests, each holding 40 balls. (See an explicit description of the Bengal opium manufacture, and the mode of its official supervision, by W. C. B. Eatwell, Pharm. Jour. Trans., Vol. XI, 1851, pp. 269, 306, and 359; also J. R. Jackson, Pharm. Jour. Trans., Vol. I, 1871, p. 782.) This opium is a rather inferior grade, owing to possible fermentation, during the several months which are consumed in its manufacture. It contains only from 3 to 4 per cent of morphine, and about as much narcotine. A better grade is the Patna garden opium (see Guibourt, Hist. d. Drogues, 1876), which is said to reach Smyrna opium in quality. Malwah opium is made in Central India; its cultivation is free, only the product has to pay a tax upon delivery at Bombay, from whence it is shipped. It is formed in balls of about 300 grammes each. Malwah opium has been most esteemed by the Chinese. The opium intended for export to China, is called in India provision opium; that grown for local consumption is called excise opium (Benares Akbari). In recent years the latter yielded to the Indian government an annual revenue of about £1,000,000. During 1893 the value of the total exports of opium from India was about £8,000.000 (P. L. Simmonds, Amer. Jour. Pharm., 1895, p. 325). The cultivation of opium in other parts of India is insignificant. In the Madras presidency it is prohibited.

CHINESE OPIUM.—Opium was hardly known in China until the importations from India began, about 1780, notwithstanding the protests of the Chinese government. The drug being admitted into China since 1858, the Chinese production has been greatly stimulated by the high import duties placed upon the foreign drug. The Chinese government, although without avail, has, from time to time, issued proclamations placing the penalty of death upon the cultivation of opium, "which covers the nourishing rice-fields with useless and harmful plants" (Scherzer, loc. cit.). The chief provinces where opium is now grown are Ssuchuan and Yünnan, and in recent years the import into Shanghai from the western provinces seems to correspond with the decrease in the imports of the English drug (see statistics in Pharm. Jour. Trans., Vol. III, 1896, pp. 465 and 532). The Chinese opium was at one time inferior to the English opium, while also much cheaper, 20 to 50 per cent; but its quality has since improved. (For some interesting information regarding the smoking of opium by the Chinese, see editorial in the Pharm, Jour. Trans., Vol. XIII, 1882, p. 225; G. Bird wood, ibid., Vol. XII, 1881, p. 500; and S. Culin, Amer. Jour. Pharm., 1891, p. 497.)

EGYPTIAN OPIUM.—This is now used only by the natives, and is produced at Akmim, and at Assiout, both on the river Nile. Mr. Martindale (Amer. Jour. Pharm., 1889, p. 187) reports the former to contain 7.24 per cent, the latter only 0.6 per cent of morphine.

AUSTRALIAN OPIUM.—Poppy was first grown in Australia in 1871, and is sown and cultivated in the same manner as Smyrna opium, except that, on account of the antipodal seasons, sowing is done at three different times in the months of June and July, instead of from November to February, as practiced in Asia Minor. An analysis of Bacchus Marsh opium showed 10.65 per cent morphine, and 6.48 per cent narcotine (W. E. Matthews, Amer. Jour. Pharm., 1888, p. 45).

EUROPEAN OPIUM.—Poppy has been planted in various parts of Germany; but while it yields a high percentage of morphine (8.7, 14.8, and 22 per cent in Würtemberg opium, E. Dieterich, 1888), the culture of opium is not promising on account of the great value of ground, and the large cost of labor. Guibourt (Jour. Pharm. Chim., 1862, p. 199) reports on a number of French opiums of high percentage in morphine (from 12 to 22.8 per cent).

AMERICAN OPIUM.—Attempts have been made to cultivate poppy in Mississippi, Louisiana, Virginia, Tennessee, Illinois, California, and other states; but while an opium rich in morphine may be obtained from the capsules, the labor it requires would make the cultivation unprofitable. Poppy grown in New Ulm, Minn., yielded 15.23 per cent of morphine, 0.325 per cent narcotine, 0.416 per cent codeine, and 3.5 per cent meconic acid (E. Wescheke, Amer. Jour. Pharm., 1886, p. 407).

Pharmaceutical Preparations of Opium.—(See also other opium preparations under their respective heads.) OPII PULVIS (U. S. P.), Powdered opium: "Opium dried at a temperature not exceeding 85° C. (185° F.), and reduced to a very fine (No. 80) powder. Powdered opium, for pharmaceutical or medicinal purposes, when assayed by the process given under opium, should yield not less than 13 nor more than 15 per cent of crystallized morphine. Any powdered opium of a higher percentage may be brought within these limits by admixture with powdered opium of a lower percentage, in proper proportions"—(U. S. P.).

OPIUM DEODORATUM (U.S. P.), Deodorized opium, Opium denarcotisatum (U. S. P., 1880), Denarcotized opium.—"Powdered opium, containing 13 to 15 per cent of morphine, one hundred grammes (100 Gm.) [3 ozs. av., 231 grs]; ether, fourteen hundred cubic centimeters (1400 Cc.) [47 fl℥, 163♏︎]; sugar of milk, recently dried and in fine powder, a sufficient quantity to make one hundred grammes (100 Gm:) [3 ozs. av., 231 grs.]. Macerate the powdered opium with seven hundred cubic centimeters (700 Cc.) [23 fl℥, 321♏︎] of ether, in a well-closed flask, during 24 hours, agitating from time to time. Pour off the clear, ethereal solution as far as possible, and repeat the maceration with two further portions of ether, each of three hundred and fifty cubic centimeters (350 Cc.) [11 fl℥, 401♏︎], first for 12 hours, and the last time for 2 hours. Collect the residue in a weighed dish, dry it, first by a very gentle heat, and finally at a temperature not exceeding 85° C. (185° F.), and mix it thoroughly, by trituration, with enough sugar of milk to make the product weigh one hundred grammes (100 Gm.) [3 ozs. av., 231 grs.]"—(U. S. P.). The purpose of this process is to remove narcotine from opium by means of ether, in which it is soluble, while morphine is nearly insoluble (see Morphina).

Adulterations and Tests.—In addition to the adulterants before enumerated, opium may be falsified with stones, sand, clay, gypsum, litharge, starch, gum Arabic, ashes, fragments of poppy capsules, resins, wax, licorice juice, etc. Some of these additions may be recognized by closer ocular or microscopic examination; others may be more difficult to detect. Inorganic matter will be indicated by the increase in ash, of which good opium yields not more than 5 or 6 per cent. Gum would be indicated by a gelatinous consistency of a hot aqueous infusion of opium; starch by the iodine test; licorice extract by a dark coloration of the moderately diluted aqueous infusion.

The presence of morphine alone in a vegetable extract does not suffice to prove the extract to contain opium; it must also give the tests for meconic acid. This is done in the following manner: Filter the aqueous infusion of the supposed opium, treat it with excess of solution of acetate of lead, and set aside in a tall vessel for the precipitate of meconate of lead to subside; the clear liquor holds in solution acetate of morphine. Pour off the supernatant fluid, and collect the precipitate on a filter. Test the clear filtrate for morphine by evaporating to dryness with potassium carbonate, abstracting the morphine with alcohol, and applying to it the tests as given under morphine (see Morphina). Test the precipitate for meconic acid by suspending it in water and decomposing the lead salt by a current of hydrogen sulphide gas or with diluted sulphuric acid; filter, and in the first case, expel the excess of gas by warming on the water-bath, and apply to the solution the tests for meconic acid (see Meconic Acid, p. 1413 [a few paragraphs down]).

Purchasers of opium in former years relied almost exclusively on external characters, as color, odor, taste, texture, moisture, and freedom from obvious admixture. In recent years, the quality of a given opium is judged mainly by its morphine contents, ascertained by reliable assay methods.

As stated above, the U.S. P. demands good opium to contain, in its natural, moist condition, not less than 9 per cent of morphine. This is to be ascertained by the following official process:

ASSAY OF OPIUM (U. S. P.).—"Opium, in any condition to be valued, ten grammes (10 Gm.) [154.3 grs.]; ammonia water, three and five-tenths cubic centimeters (3.5 Cc.) [57♏︎]; alcohol, ether, water, each, a sufficient quantity. Introduce the opium (which, if fresh, should be in very small pieces, and if dry, in very fine powder) into a bottle having a capacity of about 300 Cc., add 100 Cc. of water, cork it well, and agitate frequently during 12 hours. Then pour the whole as evenly as possible upon a wetted filter having a diameter of 12 Cm., and, when the liquid has drained off, wash the residue with water, carefully dropped upon the edges of the filter and the contents, until 150 Cc. of filtrate are obtained. Then carefully transfer the moist opium back to the bottle by means of a spatula, add 50 Cc. of water, agitate thoroughly and repeatedly during 15 minutes, and return the whole to the filter. When the liquid has drained off, wash the residue, as before, until the second filtrate measures 150 Cc., and finally collect about 20 Cc. more of a third filtrate. Evaporate in a tared capsule, first, the second filtrate to a small volume, then add the first filtrate, rinsing the vessel with the third filtrate, and continue the evaporation until the residue weighs 14 Gm. Rotate the concentrated solution about in the capsule until the rings of extract are redissolved, pour the liquid into a tared Erlenmeyer flask having a capacity of about 100 Cc., and rinse the capsule with a few drops of water at a time, until the entire solution weighs 20 Gm. Then add 10 Gm. (12.2 Cc.) of alcohol, shake well, add 25 Cc. of ether, and shake again. Now add the ammonia water from a graduated pipette or burette, stopper the flask with a sound cork, shake it thoroughly during 10 minutes, and then set it aside, in a moderately cool place, for at least 6 hours, or over night.

"Remove the stopper carefully, and, should any crystals adhere to it, brush them into the flask. Place in a small funnel two rapidly acting filters, of a diameter of 7 Cm., plainly folded, one within the other (the triple fold of the inner filter being laid against the single side of the outer filter), wet them well with ether, and decant the ethereal solution as completely as possible upon the inner filter. Add 10 Cc. of ether to the contents of the flask, rotate it, and again decant the ethereal layer upon the inner filter. Repeat this operation with another portion of 10 Cc. of ether. Then pour into the filter the liquid in the flask, in portions, in such a way as to transfer the greater portion of the crystals to the filter, and, when this has passed through, transfer the remaining crystals to the filter by washing the flask with several portions of water, using not more than about 10 Cc. in all. Allow the double filter to drain, then apply water to the crystals, drop by drop, until they are practically free from mother water, and afterward wash them, drop by drop, from a pipette, with alcohol previously saturated with powdered morphine. When this has passed through, displace the remaining alcohol by ether, using about 10 Cc., or more if necessary. Allow the filter to dry in a moderately warm place, at a temperature not exceeding 60° C. (140° F.), until its weight remains constant, then carefully transfer the crystals to a tared watch-glass, and weigh them.

"The weight found, multiplied by 10, represents the percentage of crystallized morphine obtained from the opium"—(U. S. P.).

The characteristic feature of the foregoing process, which is practically that of Dr. E. R. Squibb (see Ephemeris, 1888, p. 967) consists in precipitating the morphine, by aqua ammoniae, from a hydro-alcoholic solution of about 30 per cent alcohol. The addition of the latter has the purpose of keeping the coloring matter dissolved. The addition of alcohol is objected to, by E. Dietrich and others, because alcoholized mother liquors will retain a certain quantity of morphine in solution, at least more than an aqueous mother liquor would hold; the addition of alcohol also facilitates the precipitation of calcium meconate which will be added to the weight of, and counted as, morphine. It is believed, however, that these opposite sources of error about balance each other. Ether is used in the assay in order to remove narcotine, which is soluble, while morphine is nearly insoluble, in this solvent (see Morphina).

The U. S. P. assay process lacks directions for testing the purity of the morphine obtained. The degree of its purity may be judged by several methods: (1) Titration with volumetric acid solutions; (2) incinerating the assay morphine, calculating the weight of the ash as calcium meconate, and deducting this value from the weight of morphine employed; (3) treating the assay-morphine with 100 parts of lime-water and weighing the non-morphine residue; (4) separating the morphine from inorganic salts by means of alcohol. Regarding these methods, and the desirability of perfecting the U. S. P. assay method in general, see L. F. Kebler, Amer. Jour. Pharm., 1895, p. 398, and 1896, p. 257; also F. X. Moerk, ibid., 1894, pp. 433-446, and 1897, pp. 343-350. The German Pharmacopoeia, following Dieterich's process (see Pharm. Centralh., 1886, p. 541, and 1890, p. 597), avoids the use of alcohol. An aqueous infusion of opium (which contains the morphine as sulphate and meconate) is first treated with just sufficient diluted ammonia water to precipitate the bulk of narcotine; the filtrate is then treated with ether and sufficient ammonia water to precipitate the morphine.

Among the recently proposed methods for the assay of opium, the volumetric method of H. M. Gordin and A. B. Prescott (Pharm. Archives, 1898, p. 121) stands conspicuous. Its principle is as follows: The opium alkaloids are set free by trituration of the opium sample with a mixture of stronger ammonia water and alcohol, of each 1 part, ether 4 parts, and chloroform 2 parts. The free narcotine, papaverine, codeine, and thebaïne, are then removed by percolation with benzol, after which the morphine is taken out by percolation with acetone or pure amyl alcohol. This solvent is evaporated, the residue taken up with lime-water which completely dissolves and purifies the morphine. Filter the lime solution, acidulate it, to a very slight excess, with hydrochloric acid, and determine the morphine as periodide (C₁₇H₁₉NO₃.HI.I₃) by adding an excess of decinormal iodine volumetric solution, shaking thoroughly until the precipitate has subsided and the liquid is clear; the excess of iodine is then titrated back in an aliquot part of the liquid, with decinormal sodium thiosulphate solution. One Cc. of decinormal iodine solution corresponds to 0.00947937 gramme of morphine. This method gives higher results than the U. S. P. assay method (see Proc. Amer. Pharm. Assoc., 1898, p. 372).

Chemical Composition.—The characteristic constituents of opium are its alkaloids, of which about 20 have been discovered. They occur mostly combined with sulphuric acid and with meconic acid; narcotine, being a weak base, seems to occur in the free state. Some opiums do not contain all these alkaloids. For example, specimens of French opium, according to Decharme (1862), were free from narcotine, narceïne and thebaïne. E. Kauder (Archiv der Pharm., 1890, pp. 419-431) found eleven crystallizable alkaloids in opium, viz.: morphine, codeine, narceïne, narcotine, papaverine, thebaïne, and the rarer alkaloids, cryptopine (70), laudanine (20), protopine (3.5), laudanosine (1), and a new alkaloid, tritopine (2); the relative proportions of the latter being indicated by the numbers affixed. The alkaloids lanthopine, codamine, and hydrocotarnine of O. Hesse (1870 and 1871), were not observed in E. Kauder's opium material. Morphine, however, occurs in all opiums. Indifferent substances in opium are meconin (C₁₀H₁₀O₄), and meconoiosin (C₈H₁₀O₂). According to Flückiger, (Pharmacognosie des Pflanzenreichs, 3d ed., 1891, p. 182), opium contains also small amounts of caoutchouc, wax, and sugar; mucilage, not identical with gum Arabic, albumen, pectin, coloring matter, and inorganic matter (3 to 5 per cent of ash). Starch, fat, and tannin, seem to be absent. The following table enumerates the peculiar constituents of opium:

The separation of these substances is effected, according to the method of Gregory, Robiquet, and Anderson (see Morphina). (For details, see Husemann and Hilger, Pflanzenstoffe, p. 669.) An analytical scheme of separating opium alkaloids has been devised by P. C. Plugge (Amer. Jour. Pharm., 1887, p. 511, and Pharm. Jour. Trans., Vol. XVIII, 1888, p. 692).

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King's American Dispensatory, 1898, was written by Harvey Wickes Felter, M.D., and John Uri Lloyd, Phr. M., Ph. D.