Opium

Opium (FUP), Opium (Laudanum, Meconium, Lac Papaveris, Succus Thebaicus), the dried milky juice that exudes from incisions made on the unripe capsules of the Papaver somniferum L. poppy plant. The word opium corresponds to the Greek opion, meaning poppy juice, which is a diminutive form of opos, meaning juice (Meconium from the Greek mekon, meaning poppy, thebaicus from Thebai, meaning Thebes). The use of O. in medicine dates back to ancient times. There are indications that the ancient Egyptians and Hindus were familiar with it or similar preparations derived from the poppy. As for Greek medicine, although Hippocrates knew the soporific properties of the white poppy, which he classified among the anti-diarrheal uterine remedies, he did not use poppy preparations as analgesics. The first Greek physician to use O. was Theophrastus, a pupil of Aristotle. Pliny already used the term O. in its modern sense, described in detail the preparation of the drug and spoke of its adulteration. Galen described the symptoms of both acute and chronic opium poisoning. Medieval European physicians made little use of O., fearing its poisonous properties. Arab physicians used it (under the name afjun, a corrupted word from opium) mainly against cough. Opium acquired special importance as a therapeutic remedy from the time of Paracelsus and his disciples, among whom Sylvius de le Boë (Sylvius de le Boë) even earned the nickname "Doctor opiatus." He also coined the following aphorism: "I would not want to practice medicine if I were deprived of O." Sydenham (Sydenham; 1624-68) rigorously justified the use of O. in medicine. In our pharmacopoeia (Ph VII) only one variety of poppy is listed as the source of O.-Papaver somniferum glabrum. According to Boissier, in addition to this variety, which is mainly cultivated in Asia Minor and Egypt, O. is obtained from the variety Papaver somniferum setigerum, which grows wild in the Peloponnese, on the island of Cyprus and Corsica, and Papaver somniferum album, which is mainly cultivated in Persia. According to Hager, it is currently believed that all varieties of poppy that yield O., both wild and cultivated, represent one species, Papaver somniferum L., and that the cultivated forms originated from the wild Mediterranean form. In this connection, three varieties are distinguished: α-Papaver somniferum setigerum O.S., which grows wild, and the cultivated β-Papaver somniferum nigrum D.C. and γ-Papaver somniferum album D.C. The variety nigrum differs little from setigerum; both usually have purple flowers, opening capsules, and dark seeds. Papaver somniferum album usually has white flowers, sometimes with dark spots at the base of the petals, rarely pink, closed capsules, and white seeds. In Boissier's variety glabrum, which (according to Tschirch) belongs to Papaver somniferum nigrum, the flowers are usually purple, sometimes white, as well as all transitional shades to violet coloring. The color of the seeds is also diverse, ranging from white to bluish-black. The classification of poppy varieties is unclear, as transitional forms exist. According to the latest research by N. A. Bazilevskaya, the origin of the varieties of Papaver somniferum is different from the opinion expressed above, which is why this species should be divided not into varieties but into races. The variety album is the main source of O. in almost all countries cultivating poppy. At present, poppy is cultivated in significant quantities for obtaining O. 1) in Asia Minor and on the Balkan Peninsula, 2) in Persia, 3) in East India, 4) in China, 5) in Egypt (very little), 6) in Kazakhstan, 7) there have been attempts to cultivate poppy in Europe (Germany, Austria, France), Algeria, the United States of North America, Australia (these attempts had no practical success). The seeds of Papaver somniferum do not contain alkaloids, which can be found in young plants 14 days after germination. Then the amount of alkaloids increases until flowering is complete, and this amount is directly dependent on the soil and lighting. With the ripening of the seeds, the amount of alkaloids decreases. According to Kerbosch, the first alkaloid to appear in plants is narcotine, followed by codeine, morphine, papaverine, narceine, and thebaine, with narcotine appearing in significant amounts as early as the third day. In flowering plants, narcotine, codeine, morphine, and papaverine are found in all organs. The amount of morphine in the milky juice depends on the variety of the plant. The content of alkaloids in general and of morphine in particular varies in the unripe capsules. The capsules contain the same alkaloids and indifferent substances as O. Fresh milky juice, in addition to the alkaloids of O., contains wax (in the form of an emulsion), protein, pectin, mucilaginous substances, rubber, calcium, magnesium, and potassium salts in the form of sulfates and phosphates. The juice has an acidic reaction and contains neither tannin nor starch. To obtain O., the collection of which is carried out twice a year-in autumn and spring, not too deep incisions are made on the unripe capsules, calculated so as not to penetrate inside the capsule, where the milky juice could flow out and thus be lost for obtaining O. The latter, with proper incisions, flows onto the surface of the capsule. Incisions are made in the evening. During the night, the milky-white juice dries and thickens, acquiring a honey-like consistency and a somewhat darker color. The juice is usually collected in the morning, about ten hours later, but no later than 24 hours after the incisions are made. Incisions are made every 3 days, up to seven times (usually no more than 3 times). Further processing is not the same in all countries. In Asia Minor, from which the O. mainly used as a pharmaceutical product is obtained, the collected thickened juice is kneaded and formed into lumps of various sizes, which are wrapped in poppy leaves and further dried in the shade. Then the lumps are sprinkled with dry seeds of sorrel (Rumex patientia, var. orientalis). For the varieties of poppy in Asia Minor, each capsule (there are 5 to 20 on a plant) yields about 0.02 of opium. For European trade, the varieties obtained from the Near East are of main importance. 1. Turkish O. enters trade in two varieties: a) Smyrna O. (O. smyrniacum) is mainly produced in Asia Minor and enters the market through Constantinople and Smyrna and from there to Europe via Trieste. It contains the largest amount of morphine and is considered a pharmaceutical product, b) Constantinople O. is imported through Constantinople to London, Hamburg, and Rotterdam; also a good product. It is obtained on the shores of the Black Sea. The lumps of Smyrna and Constantinople O. weighing 250.0-700.0, rarely up to 1,000.0, are usually sprinkled with sorrel seeds and wrapped in poppy leaves. The lumps are brown and hard on the outside, yellowish and soft inside. The morphine content in both varieties is 7-15%. Upon careful examination of the cross-section of the O. lumps, especially with the help of a magnifying glass, it can be seen that the mass of O. consists of grains (O. smyrniacum) of different sizes and shapes, forming a common mass, and that O. contains grayish inclusions consisting of surface particles of poppy heads. When dried, the color difference of these inclusions from the color of O. becomes more noticeable. In addition to the preparation mentioned, there are also: 2. Egyptian, or Theban, or Alexandrian O. (now little used). 3. Persian O.; mainly consumed locally. The varieties imported into Europe have various forms (sticks, small lumps wrapped in paper, etc.), contain up to 15% or more morphine and are used to obtain this alkaloid. 4. East Indian O. is consumed in Asia and not imported to Europe. Morphine content 3-10%. It exists in several varieties, such as Benares, Patna, Malwa-opium, etc. 5. Chinese (the cultivation of opium poppy in China is officially prohibited) is consumed locally. 6. Greek O. often contains more than 10% morphine. 7. Bulgarian or Macedonian O. is sold in lumps weighing 100-200 g. Morphine content more than 10%. Although other European varieties (French, German) contain a lot of morphine (up to 20 percent or more), they have no commercial value, just like the American and Australian varieties. In the markets of the Balkan Peninsula, a second-grade O. is sometimes sold, obtained from Glaucium luteum (Papaveraceae), which does not contain morphine and other main alkaloids of opium, but has some narcotic effect. Good varieties of O. have a characteristic, not unpleasant narcotic odor and a bitter taste. Density about 1.3. Water and weak alcohol dissolve about half of O. by weight, forming a brown solution of acidic reaction. Upon adding a drop of diluted ferric chloride solution to 10 cm³ of filtered aqueous extract of O. (1:10), the liquid extract turns red (meconic acid). O. should not have a musty or rancid odor or a salty or sweetish taste. In the cross-section of O., sand, starch, seeds, or other foreign substances should not be noticeable.

Good grades of O. harden upon storage, while poor grades, with the addition of vegetable oils or honey, conversely soften. All preparations of O. must be made from O. powder, which is obtained by drying in drying cabinets at a temperature not exceeding 60°, followed by trituration and sifting. The O. powder should have a light-brown color. 2 g of O. when dried at 100° to constant weight should not lose more than 0.3 g, and 2 g of powder when similarly dried should not lose more than 0.16 g. Upon incineration and calcination of the resulting dry residue, no more than 0.12 g of ash should remain. O. according to F VII should contain 10% morphine. Composition of O. Asian O. contains about 20 different alkaloids, of which the main ones are: morphine, narcotine, papaverine, thebaine, codeine, and narcine; 3 indifferent substances: meconin, meconizine, and opiopine; acids: meconic (4%), lactic (1.25%), sulfuric, and acetic; coloring substances, saccharine substances, mucus, resin, rubber-like substances, gum, wax, fat, protein substances, fragrant substances, and salts of inorganic bases. According to some research, O. contains from 0.2 to 0.3 ammonia. Content of alkaloids in opium (in %) (according to Wiesner). Alkaloid % Alkaloid o/ /O Morphine . . . 9 (up to 23) Cryptopine . . . 0.08 Narcotine . . Pseudomorphine . 0.02 (0.75-9.6) Laudanine . . . 0.0! Papaverine . 0.8 Laudanopine . . . 0.006 Thebaine.... 0.4 Protopine . . . Codeine . . 0.5 Codamine . . . . 0.002 (0.2-0.8) Tritopine . . 0.0015 Narcine . . . 0.2 Laudanosine . . 0.0008 In addition, the following alkaloids are found in O.: hydrocotarnine, xanthine, laudanidine, cotarnine, gnoscopine, oxynarcotine, and readine. The alkaloids of O. are chemically divided into three groups (according to Cloetta): 1. Phenanthrene derivatives - morphine, pseudomorphine, codeine, thebaine. 2. Isoquinoline derivatives - papaverine, laudanosine, laudanine, laudanidine, cryptopine, protopine, narcotine, narcine (oxynarcotine), xanthine (papaveraldine). 3. Alkaloids whose constitution is not precisely determined: codamine (probably of the isoquinoline group), meconidine, laudanopine, tritopine, ionine, pseudopapaverine, papaveramine, readine. Of the listed alkaloids, a considerable part, both due to their negligible content in O. and their weakly expressed pharmacological action, can hardly have any noticeable influence on the general effect of opium action. Among the active alkaloids, morphine occupies the most important place, which mainly determines the pharmacodynamics of O. (see Morphine, Codeine). The most important aspects of the very complex action of morphine reduce to analgesia, the dual effect on various parts of the central nervous system, on the one hand depressing and hypnotic, on the other hand exciting the motor centers, and the effect on the intestine, and this dual effect on the central nervous system and the effect on the intestine in different animals show much diversity. On the intestines of dogs, rabbits, and cats, morphine causes (especially sharply on the isolated intestinal loop) an increase in tone and strengthening of movement; in guinea pigs on the same object, the opposite phenomena occur. Codeine differs mainly in its weaker analgesic and hypnotic action and its more pronounced exciting action on the central nervous system, causing an increase in reflexes. On the respiratory center, codeine exerts a similar but weaker calming effect than morphine. The effect on the intestine is also generally analogous to the action of morphine, although weaker. On the isolated intestine of a rabbit or dog, codeine has an exciting effect, while on that of a guinea pig it has a depressing effect (but weaker than morphine). Thebaine (methyl ester of codeine, or dimethylmorphine) acts on the central nervous system even more excitingly than codeine, which is why it is usually classified in the strychnine group according to its action. In humans, in doses that do not cause convulsions, it has a weak hypnotic effect. On the isolated intestine of a rabbit, it acts (according to the experiments of most authors) similarly to morphine and codeine - in an exciting manner. It also initially excites the isolated intestine of guinea pigs. Pseudomorphine, which is the ester of oxidized morphine and also called oxymorphine, is obtained by weak oxidation of morphine, according to the formula: 2C₁₇H₁₈N0₃+NO = [C₁₇H₁₈N0₃]₂ + 4-H₂0. When administered orally or under the skin, it is pharmacologically inactive. Its poisonous effect is only observed when introduced into the blood. In dogs, vomiting, bloody stools, and paralysis of respiration are observed. Of the isoquinoline group alkaloids, papaverine is contained in O. (see). Laudanosine is a tetanic poison, causing in animals increased respiration, restlessness, salivation, mydriasis, and paroxysmal convulsive tremors, passing into general tetanus. Laudanine, the methyl ester of which is laudanosine, is contained in O. in negligible amounts and belongs to the group of convulsive poisons. Laudanidine is an isomer of laudanine and is also contained in O. in very small amounts. Cryptopine causes excitement in dogs, in large doses mydriasis and sleep with respiratory depression; it also depresses the activity of the heart. In humans, dilation of the pupils and a hypnotic effect three times stronger than that of narcine and much weaker than that of morphine have been observed. Protopine (macleine, fumarin) causes convulsions in warm-blooded animals. It affects the circulation, causing first an increase and upon repeated administrations a fall in blood pressure. It has a local anesthetic action similar to cocaine. Narcotine (opion, narcosine) has a weakly expressed narcotic and distinct tetanic action on warm-blooded animals. It excites respiration; it causes a slowing of the heart rate, acting on the cardiac ganglia. In humans, a very weak narcotic effect is observed, and when taken orally, a delay in peristalsis. It is little poisonous for humans. Hydrocotarnine exhibits tetanic and some narcotic action, similar to the action of substances of the codeine group, but less poisonous. Gnoscopine is the racemic isomer of cotarnine, obtained from the decomposition of narcotine. Pharmacologically, it is similar to narcotine but weaker. Narcine. Contrary to the data of previous authors who attributed very pronounced hypnotic properties to narcine (Cl. Bernard), more recent research conducted with a purer product showed a very weak pharmacological action of this alkaloid. Thus, the administration of up to 20 g to a rabbit had no effect. Xanthine, or papaveraldine (also found in O. in small amounts) is one of the derivatives of papaverine. Of the alkaloids whose constitution is not precisely known, tritopine is pharmacologically similar to thebaine, laudanine, and laudanosine, causing in animals strychnine-like convulsions. Readine is pharmacologically inactive. Codamine, meconidine, laudanopine are contained in O. in very small amounts. Even from the consideration of the main pharmacodynamic properties of the alkaloids belonging to the above-mentioned groups (phenanthrene and isoquinoline), it is clear that such a grouping by no means determines all aspects of the action of the alkaloids of O., and in the isoquinoline group there are a number of alkaloids (laudanine, laudanosine, tritopine) similar in action to codeine. Perhaps only in terms of the action on the intestine (and generally on the smooth muscle) of certain species of animals (dog, cat, rabbit), the mentioned chemical grouping corresponds pharmacodynamically, since the alkaloids of the phenanthrene group act excitingly on smooth muscle, while the alkaloids of the isoquinoline group act paralyzingly (Popper, Macht). From an exclusively pharmacodynamic point of view, Gottlieb divides the opium alkaloids into 3 groups, the representatives of which are morphine, codeine, and protopine. If we arrange the alkaloids of opium according to the intensity of their various actions (corresponding to the main aspects of morphine's action), we get the following series. By analgesic action (according to Starkenstein) By narcotic and tetanic action (according to Starkenstein) By the strength of toxic action on humans (according to Rabuteau) Morphine Papaverine Codeine Narcotine Narcine Thebaine Morphine Papaverine Codeine Laudanosine Laudanine Thebaine Morphine Codeine Thebaine Papaverine Narcine Narcotine According to the latest data, this order should be changed in the sense that narcine should be placed last in terms of toxicity. From the comparison of all the data presented, it follows that the effect of other opium alkaloids on the effect of morphine is very complex; this is the essence of the pharmacological problem of O., which aims to clarify the relationship between the action of O. and the action of morphine. In relation to some aspects of morphine's action, individual alkaloids are its synergists, while in relation to others they are antagonists. The matter is complicated by the fact that the synergism of alkaloids can manifest in the summation of their action (additive action) as well as in their mutual potentiation. The experiments conducted to clarify how the alkaloids of O. act in this sense gave sharply different results among various authors, showing that both types of synergism can occur under different conditions.

It should also be borne in mind that the effect of the poison's action depends to a large extent on the state of excitation or depression of the organ. Therefore, an organ already excited or depressed by a particular alkaloid reacts differently to its antagonist than an organ in a state of normal functional equilibrium. Ultimately, the effect of all opium alkaloids must naturally differ not only quantitatively but also qualitatively from the action of morphine. In addition to the alkaloids, opium contains, as already indicated above, a number of more or less indifferent substances, many of which have colloidal properties. This non-alkaloid part can have a dual significance in the action of opium: first, it can affect the absorption of alkaloids, and second, it can itself exert some effect on the body. The latter was attributed by some authors to meconic acid, which in experiments on animals shows some exciting effect. However, in experiments on humans, even large doses (up to 8 g) proved to be completely ineffective. The effect of colloidal substances on the absorption of opium alkaloids can be twofold: 1) delayed absorption reduces their toxicity and strength of action, 2) the same delay promotes the longer stay of alkaloids in the intestine and their action over a larger area. The latter is very important, since the effect obtained on the intestine, whether of an exciting or depressing character when exposed to various medicinal substances, depends on the number of points of the intestine on which the medicinal agent acts. The pharmacodynamics of opium as a whole, although mainly determined by the presence of morphine in it, nevertheless differs from that of the latter. The local action of opium is also weak, as with morphine, because cryptopine and protopine, which have the ability to paralyze the nerve endings of sensory nerves, are found in opium in insufficient quantity to manifest their action. The toxicity of opium for humans, as is usually assumed, does not quite correspond to the toxicity calculated from the amount of morphine it contains, and exceeds the latter. According to the pharmacopoeia, the maximum dose of morphine is 0.03, while that of opium is 1.0. Thus, with a 10% morphine content in opium, the latter is considered not 10 times, but only 3.3 times less toxic compared to the former. This was explained by the toxic effect of other alkaloids, primarily narcotine, which according to Straub's experiments on mice may also have a potentiating effect here. However, experiments on animals and clinical observations of pantopon speak for the correspondence between the toxicity of the latter preparation (containing all opium alkaloids) and its morphine content. The effect of opium on the central nervous system, according to Cushny, if one takes into account the difference in the absorption of poisons, is similar or almost similar to that of morphine. Comparative observations of the action of pantopon and morphine nevertheless indicate some exciting effect of the side alkaloids, especially at small doses. Of particular interest is this exciting (or more precisely - less narcotizing) effect in relation to the respiratory center, the depression of which is often one of the undesirable side effects of morphine. Due to the lesser depression of the respiratory center by opium, its use in children, although requiring extreme caution, is still more permissible than that of morphine. The significance of side alkaloids in the analgesic effect of opium is evidenced by experiments with apomorphine, i.e., morphine-free pantopon; 0.3-0.5 of apomorphine had in Winternitz's experiments on himself a hypnotic and analgesic effect. The excitation of heart activity, expressed in increased pulse rate and strengthened heart contractions, observed at the beginning of morphine's action, is more pronounced with therapeutic (small) doses of opium than with morphine. Pouchet points out that with a frequent and weak pulse, opium, while strengthening heart contractions, simultaneously slows the heart rhythm. Very large toxic doses weaken the activity of the heart. Blood pressure under the influence of small doses of opium first rises slightly and then falls. There occurs dilation of peripheral capillaries. Crimson spots appear on the skin. With large doses, these phenomena are more pronounced. At the same time, opium increases perspiration, especially during sleep. It should be noted that the increased perspiration observed in various pathological conditions is not increased, but rather decreased by opium. Often skin phenomena in the form of itching (pruritus opii) and various rashes are observed, which is particularly sharply expressed in cases of idiosyncrasy. These skin phenomena were attempted to be explained by the excretion of opium components by the skin. It should be noted that skin phenomena have been described with the use of both pantopon and morphine-free apomorphine. Of particular interest is the action of opium on the digestive organs. Most authors point out here the main difference in the action of morphine and opium, consisting in the fact that abnormally excited intestinal peristalsis is more powerfully inhibited by opium than by morphine. This is explained by 1) delayed absorption and the action of morphine over a large area (Schmiedeberg); 2) the synergism of side alkaloids, and experiments by Gottlieb showed that morphine-free tincture of opium stops diarrhea in cats caused by a milk diet; 3) the antagonistic action of papaverine; experiments by Paly, Macht, and others, especially conducted on the isolated intestine, showed that in a number of animals (dog, rabbit, etc.) papaverine and other main alkaloids of the isoquinoline group relax the tone and lower intestinal peristalsis, acting similarly on other organs with smooth muscles, while morphine affects these organs in the opposite direction. In the interaction of morphine and papaverine, the latter prevails, and this is also the case if its content is many times less than that of morphine. Thus, papaverine and other similarly acting alkaloids of opium, when the latter is used, neutralize in the complex action of morphine on the intestine its exciting action on tone and peristalsis. However, Trendelenburg's experiments on the intestine of guinea pigs showed that here the action of both morphine and papaverine is different, namely - both alkaloids cause relaxation of the intestine, with morphine affecting it many times more strongly. G. Meyer assumes that a similar relationship exists for the human intestine as well. Thus, the above data on the antagonistic interaction of papaverine and morphine, experimentally proven for the intestine of the rabbit and dog, cannot be considered finally established for the human intestine. Hesse explains the stronger action of opium on the intestine compared to morphine by the presence of codeine in it. However, Trendelenburg's experiments on the cat's intestine contradict such an interpretation. In view of the difference in the action of morphine on the intestines of various animal species and the difficulty therefore of transferring experimental data obtained on animals to humans, experiments conducted on humans are of particular interest. Experiments by Ganter, in which the movements and tone of the intestine were determined by means of a balloon introduced into it, showed that the constipating effect of opium (and morphine) depends on the decrease in excitability of the intestinal wall with a decrease in the height of individual contractions, but with a simultaneous increase in tone. Since this effect depends on the influence of the drug on smooth muscles, the effect of opium as a more slowly absorbed substance should be stronger than that of morphine. The action of opium on the secretory function of the digestive apparatus is close to that of morphine. Here also there is observed depression of the secretion of all glands, except the gastric glands, where opium, like morphine, causes an increase in secretion some time after food intake. Similarly, the action of opium on the autonomic nervous system and metabolism is similar to that of morphine. Although opium itself when administered subcutaneously to rabbits causes hyperglycemia, according to experiments by Danielson, it does not weaken but increases the effect of insulin in these animals. In acute opium poisoning, the same symptoms are observed as in morphine poisoning, but they develop more slowly due to slower absorption. In addition, the phenomena of nausea and vomiting are less pronounced, and conversely, skin phenomena are more sharply expressed. In the first period, the face is crimson-red, in the second, when sleep sets in, it is pale with cyanotic spots. During poisoning, remissions are often observed, during which the patient seems to recover. Sometimes after a remission, sudden death follows. The treatment of opium poisoning is the same as for morphine poisoning. Chronic poisoning, which generally occurs more difficultly than with morphine, is observed with various methods of using opium, namely - when smoking opium and when taking it per os - opiophagy. As with morphinism, the consequences of chronic opium poisoning depend to a large extent on the predisposition of the subject.

And here too, at first, there are observed phenomena of heightened sensitivity and increased energy, and then more and more prominently there appears a disorder of nutrition, a decline in work capacity, and a change in the moral appearance of the drug addict, all of whose thoughts are exclusively focused on obtaining the poison. Smoking of opium is practiced mainly in China, where there are up to 40 million smokers, in India, Indochina, and neighboring countries. Smoking varieties of opium are prepared from the raw product, mainly Indian opium, by various methods: 1) by thickening the aqueous extract, 2) by careful heating and partial roasting (the tjandu variety). To the products obtained by both methods, various substances (residues of opium from smoking pipes, etc.) are often added. The morphine content in the tjandu variety is significantly higher, and that of other alkaloids is lower than in the raw product, which is explained by the destruction of codeine, papaverine, and narcotine and to a large extent of thebaine during roasting, since the latter alkaloids have a lower melting point compared to morphine. The technique of smoking is as follows: a piece of opium, picked up with a needle, is heated and roasted with constant rotation of the needle on a lamp until it acquires the proper plasticity. The heated piece of opium, which has turned into a ball, is placed in a pipe and pierced with a needle. The smoker, on a mat or cushion, brings the pipe to the lamp. The opium partly burns and partly sublimates, and the resulting smoke is drawn through the hole made by the needle. The pipe is smoked in one or two puffs. Such pipes the smoker smokes from 10 to 50 and even up to 100 a day. Residues of opium from pipes are carefully scraped out and sold as second-grade opium (dross, in English, scorie), which is consumed by poor smokers and opio-phages. This variety contains more morphine and smoking it is even more harmful. When smoking, a significant portion of morphine is destroyed; some authors assume that the destruction is complete and explain the poisoning from smoking by the action of sublimation products—pyrrole, pyridine, etc., up to amines and ammonia (Simon). According to others, morphine sublimates with substances that are in a colloidal state in the form of collodion. The symptomatology of poisoning from smoking is not entirely identical in different individuals: sometimes a special euphoria is observed, associated with the effect on the sphere of psychological perceptions, sometimes the stimulating effect is manifested in the sphere of volitional manifestations. At first, energy and work capacity increase; later, work, as in morphinism, becomes impossible without the introduction of the poison. It is characteristic of opium smokers, unlike alcoholic intoxication, a desire for solitude. The headaches observed in opio-phagy are more pronounced in opium smoking. In general, the phenomena caused by smoking are close to those observed in opio-phagy and morphinomania (see Morphine-morphinism). Here too, a habit to the poison is formed with the development of a need for ever-increasing doses and phenomena of deprivation when smoking is suddenly stopped. When forcibly deprived, the smoker experiences extreme suffering and is ready for any crime to satisfy his need. All this speaks in favor of the fact that the poisoning factor in smoking is also morphine. Opio-phagy—consumption of opium per os—is mainly spread in China and Persia, where this method of consuming opium is considered less objectionable than smoking. Opium is consumed both in dry form and in liquid form (in Persia as a drink prepared from poppy heads). In Europe and America, where opio-phagy has some distribution, sometimes opium is consumed in the form of a tincture. Opio-phagy is even more harmful than smoking, since the habit forms quickly and the doses consumed reach 50-100, even 250 g per day, i.e., they can exceed the maximum dose allowed by the pharmacopoeia by 750 times. The phenomena observed in opio-phagy are close to morphinomania. The phenomena from the intestines (constipation) are pronounced. Extreme emaciation, dry yellow skin, loss of sexual potency, in women—cessation of menstruation are observed. The changes in the psyche are the same as in morphinists. The phenomena of deprivation are approximately the same as with morphine: a heavy feeling, insomnia, thirst, neuralgic pains, diarrhea, sweat, and sometimes a sudden weakening of cardiac activity leading to collapse. Treatment, as in morphinism, consists of rapid or gradual withdrawal. Therapeutic application of opium. In view of the fact that the main action of opium depends on its morphine content, opium preparations are used in the same cases as morphine (see). The latter has an advantage over opium when a faster and stronger effect is required and the possibility of administering the drug under the skin is important. On the other hand, preference is given to opium when there is a fear of too strong an effect on the respiratory center (childhood) and a slower action of the drug is desirable. Opium has a special advantage over morphine as an anti-diarrheal remedy. When prescribing especially large doses of opium (the former method of treating appendicitis), to slow down absorption and prevent poisoning, the use of coating agents is recommended. Preparations. Opium, опий (Ph. VII) (on its properties see above). Opium—with a morphine content of less than 10%, according to our pharmacopoeia (Ph. VII), should not be used; in case of a higher morphine content, it is best to mix opium with opium poorer in morphine (with a morphine content of at least 7%), and if this is not possible, with the necessary calculated amount of milk sugar. Highest single dose 0.1, highest daily 0.3. Extractum Opii, extract of opium (Ph. VII). Content of anhydrous morphine 20%. Light spongy pieces of brown color, giving a turbid solution with water, strongly bitter taste. Highest single dose 0.1, daily 0.3. Tinctura Opii simplex, opium tincture (Ph. VII). Content of anhydrous morphine 1%. The tincture is transparent, dark brown in color, with a characteristic opium odor and taste. Highest single dose 1.0, daily 3.0. Tinctura Opii crocata, s. Laudanum Sydenhami, saffron-opium tincture (Ph. VII). Morphine content 1%. Prepared by infusing 15 parts of opium, 5 parts of saffron, 1 part each of cinnamon and cloves in a mixture of 70 parts of 70% alcohol and 70 parts of water. The tincture is transparent, dark yellow-brown in color, with a saffron-opium odor and a spicy taste. Highest single dose 1.0, daily 3.0. Due to the prohibition of the import of saffron, cinnamon, and cloves at present, it is not manufactured in the USSR. Tinctura Opii benzoica, Elixir paregoricum, benzoic-opium tincture (Ph. VII). Morphine content 0.05%. Contains anise oil 0.5%, camphor 1%, benzoic acid 2%, opium tincture 5%. The tincture is transparent, yellowish-brown in color, with a camphor-anise odor, a sweet-spicy taste, and an acidic reaction. Dose per administration 10-15 drops. Guttae Inosemzowi, drops of Inozemtzev—see Inozemtzev drops. Guttae Thielmanni, drops of Thielmann. Composition: Olei Menthae 5.0, T-rae Ipecac. 5.0, T-rae Opii 2.5, T-rae Valer. aether. 10.0. There are also other similar prescriptions. Dose 10-50 drops. Pulvis Doveri—see Dover's powder. Mixtures of opium alkaloids. Pantopon—see Pantopon. Orop, a mixture of opium alkaloids, except morphine, in the form of hydrochlorides. Powder partly crystalline, partly amorphous. Dose—as for opium. Laudanop, a mixture of hydrochlorides of the 6 main alkaloids of opium. White powder, soluble in water. Dose 0.02 internally and under the skin. Laudopan dr. Haas, laudopan of Dr. Haas, a mixture of meconic acid salts of the therapeutically active main alkaloids of opium, dissolved in water. Dose—as for pantopon. Sirupus Papaveris, s. Simpus diacodii, syrup of poppy heads. Used as a mild narcotic (in children) by the teaspoonful per administration.

A. Likhachev. Opium as a Social Problem. Opium is one of the oldest narcotics used by humanity. The cultivation of opium for narcotic purposes dates back to prehistoric times. The ancient Greco-Roman writers considered Greece, the islands of the Archipelago, and Asia Minor as its homeland. Further to the east, opium was apparently carried by the Arabs; it penetrated India during the period of its conquest by Muslims, although there are earlier indications of the use by Hindus of certain substances that caused a 'peaceful sleep' and 'painless death'. The Mughals who conquered India made opium cultivation their monopoly, which was later appropriated by the English conquerors (East India Company). Opium penetrated China in the 7th or 8th century, but at that time it did not play a significant role as a narcotic. Only under one of the first emperors of the Mongol dynasty, Kublai Khan (late 13th century), who conducted extensive conquests (with India, Annam, etc.), did opium penetrate China and begin to be used there for narcotic purposes (mainly per os). The Ming dynasty that succeeded the Mughals prohibited the use of opium, but in the tribute collected by the emperors, 200 cati (cati = 650 kg) of opium for the emperor and 100 for the empresses are listed: a quantity that clearly exceeded possible medical needs. Until the mid-17th century, the Chinese obtained opium from India, first as a medicinal substance. From this time, opium began to be used in the form of smoking for purposes of narcosis, and its cultivation began in China itself. At the end of the 17th century, tobacco smoking was prohibited in China, which gave a significant impetus to the growth of opium smoking. In 1729, an imperial decree prohibiting the cultivation and consumption of opium was published. As a result, poppy plantations decreased, but the import of opium from abroad, especially from India, sharply increased: thus, in 1773, the East India Company imported up to 6,000 chests of opium into China. Subsequently, the effect of opium on the population proved so detrimental that the government had to vigorously enforce anti-opium laws, severely punishing not only for trade but also for smoking opium. However, the smuggling of opium did not cease, and the Chinese government had to resort to violent measures. 20,000 chests of opium, transported by the English, were confiscated and sunk at sea, and trade with them was stopped (1839). Then the English declared to China the famous 'opium war,' from which they already strictly protected their own country at that time. This war—one of the most blatant attacks by imperialists on China—ended in 1843 with the Treaty of Nanking, by which Hong Kong was ceded to England, for which some restriction on the import of opium from India was formally provided. However, in 1843, a second war with England broke out, to which France and SAS1P joined. This war ended with a brief peace (1853), after which the third war occurred. By the peace treaty (1860), the import of opium into China was permitted without any restrictions. The Chinese government was only allowed to increase the duty on opium, i.e., to participate in the profits of Western traders. The right to import opium into China passed from the East India Company to the hands of the British government. Opium consumption in China began to grow rapidly, at the same time the area of poppy plantations within the country increased, as did the number of opium dens, etc. In 1911, the government issued a decree which provided for the gradual reduction of poppy plantations and the import of opium, so that within 10 years the production and trade of opium would be stopped throughout the country. The revolution and the continuous civil wars that followed facilitated the import of opium by foreigners, for which numerous concessions, inaccessible to Chinese authorities, served as a base. Opium now became an important source of income in the hands of various military groups (taxes, customs). In brief periods of strengthening of one or another 'central' authority, weak attempts were made to issue and enforce anti-opium laws, however, the connection of these governments (Peking, Nanking) with foreign capitalist powers did not allow the adoption of serious and active measures despite the sharply negative attitude of the masses to opium and its distributors. The 'Anti-Opium Society' formed in 1925 quickly enrolled up to 5 million members. According to the chairman of this society, Bingham-Dan, drug addiction in China is fed from three sources: 1) domestic cultivation of opium, 2) import of opium from abroad (India and Persia), and 3) import of opium alkaloids, especially morphine and heroin, from Europe and Japan. In 1928, there were 36 large opium warehouses on the French concession in Shanghai, and the police received up to 150,000 dollars a month for its indulgent attitude to these warehouses. The Dutch act even more openly in their colonies—on Java, Sumatra, etc., where, after several weak attempts at prohibition, they declared opium trade their monopoly. On the island of Java, in the city of Batavia, a special factory was built for processing raw opium delivered from India into smoking opium, which is sold in numerous opium dens rented from the Dutch authorities, operating there quite legally alongside brothels. Opium smoking is most widespread in the countries of eastern and central Asia (China, India, Persia, Afghanistan, Indochina, the Malay Archipelago), in Turkey; _tNorth Africa (Egypt, Algeria). In Turkey and Persia, opium is often smoked in a mixture with hashish, tobacco, etc. Among Europeans and Americans, the groups most affected by opium smoking are certain population groups having contact with Eastern residents (sailors, officials), residents of port cities where many opium smokers live (San Francisco, New York, etc.). Further, separate social groups more prone to drug addiction on a social basis (medical personnel, 'bohemians', declassed). However, opium consumption by Europeans does not reach large dimensions [here, along with opium smoking, opium is taken per os, especially in the form of T-ga Opi (opiophagia)]; besides opium, Europeans have a number of opium alkaloids and preparations for narcotic purposes (morphine, heroin, pantopon, dicodid, etc.). Opium is the greatest scourge for China, where the number of opium smokers is estimated at 15 million people (the harm caused by opium to its consumer varies, depending on the doses consumed, nutritional conditions, etc.). The most important producing countries of opium are China, India, and Persia, supplying the entire Far East with their opium, as well as Turkey and Yugoslavia, supplying the opium raw material to the alkaloid industry of Europe and America. The production of the USSR (Central Asia) approximately corresponds to the growing medical needs of the country in medical opium and its alkaloids. Other producing countries should be mentioned: Afghanistan, Bulgaria, Korea, Greece, Indochina, and Japan. Opium production in Japan is rapidly growing: thus, the area of opium plantations, which was 740 hectares in 1923, increased to 1,520 hectares in 1928, with raw opium obtained being 3,551 kg in 1923 and 13,630 kg in 1928. The average morphine content in opium in 1927 was 13.83%, and in 1928—15%. In China, the cultivation of opium is formally prohibited, but it is actually carried out on a large scale. Due to the current political situation in China, there are no reliable data on its opium production. The total annual production of opium on earth, according to underestimated data from the League of Nations, amounts to about 3,300 tons, with 92.5% of world opium production falling on five main producing countries (China, India, Turkey, Persia, Yugoslavia). Only a negligible part of its production (about 1/4%) goes into the manufacture of medical preparations. The situation in the main countries in recent years is as follows. In India, opium production in 1926 was 907,089 kg, in 1927—743,759 kg, in 1928—265,222 kg. Export: in 1926—556,132 kg, in 1927—505,684 kg, in 1928—458,223 kg (official and underestimated data). Persia exported 728,654 kg and 350,685 kg of raw opium in 1926-27. In 1928, the area of opium plantations was 30,000 hectares, production was 594,000 kg, and export was 477,229 kg. Opium production is rapidly growing in Turkey, where opium plantations occupied 33,000 hectares in 1927-28, and 53,000 hectares in 1929-1930. Production in 1928 reached 400 tons. Yugoslavia produced 100 tons of opium in 1926, 55 tons in 1927, 205 tons in 1928, 38 tons in 1929, and 150 tons in 1930. Export rose from 87,539 kg in 1926 to 146,582 kg in 1928. In total, opium production, excluding China, the USSR, and Afghanistan, amounted to 1,371,563 kg in 1926, 1,085,461 kg in 1927, and 1,477,852 kg in 1928. The main importing countries, consuming opium mainly for processing into alkaloids and preparations, are the following: Import of opium (in kg). Countries Germany .... France .... United Kingdom Japan ..... Switzerland . . . 1926 G. 1927 G. 1928 G. 192 635 126 092 188 751 48 971 64 602 63 709 44 100 159 221 48 650 43 019 76 258 60 285 49 878 92 913 70 943 24 803 The vast extent of opium plantations, on the one hand, and the great development of the chemical-pharmaceutical industry, on the other, sharply counteract serious efforts to combat the production and consumption of opium for narcotic purposes, i.e., in amounts exceeding the world's medical and scientific need for opium.

In addition to the anti-narcotics legislation in effect in individual countries, which also covered O. (see Narcotics), attempts were made at international agreements for a united fight against opium smoking: control of production, export, import, processing into alkaloids and preparations, as well as coordination of legislative and administrative-police measures against illegal trade in O. In 1909, an international commission on O. was convened for the first time (in Shanghai), which produced no results. In 1911, at a new international conference in The Hague with the participation of China, Germany, the USA, Russia, France, Great Britain, Japan, Persia, Italy, the Netherlands, and Siam, a convention was developed that provided for a number of coordinated measures to regulate the production and trade of O. and other narcotics. All other countries were called upon to join the convention - most interested countries managed to do so, but in 1914 the war stopped further steps in this direction. The Versailles Peace Treaty placed the responsibility for the fight against opium smoking and other narcotics on a global scale on the League of Nations (Article 23), for which a permanent opium commission was established under the League of Nations. Ratification of the Versailles Treaty was at the same time accession to the Hague opium convention. The League of Nations convened a number of conferences on issues of O. A draft of a special convention was developed at the Geneva conference (in 1925), which ended with the demonstrative departure of the American and Chinese delegations. The last international conference on the fight against narcotics, held in Geneva in 1930, did not pay attention to the issues of production, trade, and processing of O., despite the fair indication of the Soviet delegation that it is impossible to fight the abuse of narcotics without prior settlement of the opium problem. The behavior of most governments on the opium issue is determined by the presence of opium products and industry in their countries, so attempts to fight O. are insincere and hypocritical (with the exception of China, which suffers greatly from O.). England is interested in the production of O. (India) and its sale to China; Germany, France, Switzerland, the Netherlands, etc. - in the protection of their alkaloid industry. Thus, under capitalism, an effective fight against opium smoking is impossible. The relatively active position of the USA is explained by the relatively small economic interest of this country in the issues of O. and its advantageous position as a 'friend and protector of China.' As for the USSR, by decree of August 27, 1924, the monopoly on O. was transferred to the joint-stock company AKOSPO, to which all opium planters had to surrender the entire harvest of O. on contractual terms. From 1930, this society was merged into the state organization Lectekhsyr'e, which concentrated in its hands the collection of O., as well as supplying O. raw materials to the pharmaceutical industry and trade network, which are under the leadership of Gosmedtorgprom. Thus, the concentration of production, processing, and trade (distribution) of O. in the hands of the state carried out in the USSR is a sufficient guarantee that O. is indeed used for medical and scientific purposes (which was also recognized at the last international conference on the fight against narcotics, Geneva, 1931). The concentration of O. in the hands of the Soviet government, strict anti-narcotics legislation, the absence of a private pharmaceutical industry and trade, and the insignificant development of private medical practice, along with the general change in working and living conditions - these are the main factors for the successful fight against the abuse of O. (and other narcotics) in the USSR. On the number of opium smokers, anti-narcotics legislation, etc. -- see Narcotics, Morphine, etc. A. Rapoport.