Through experience and tradition a large number of the substances used in modern medicine have been used in much the same way for centuries by primitive people throughout the world. This is true of important substances such as opium, digitalis, quinine bark, coca leaf, ergot, curare and rauwolfia, to mention but a few.
One of the first scientists who devoted his attention to a closer study of the active principles of the crude drugs was Paracelsus (1493-1541). He attempted through distillation, pyroanalysis and other alchemical processes to isolate the "quintessence "-the active principle--of opium. His crude methods failed to produce results; but he had shown the way, and other men of science in turn tackled the same problems more successfully. The introduction by the pharmacist C. W. Scheele of crystallization as a method for the purification of natural substances was of fundamental importance in this development.
I Doser Opium Mp3 Download
In the case of drugs with morphine-like effects the choice between the natural substances and synthetics goes back only a couple of decades. Although morphine and some of the secondary alkaloids of opium can now be synthesized by organic chemical methods, the poppy plant is still the source of commercially manufactured morphine and also the basic material for the semi-synthetic drugs with morphine-like effects (cf. group 2). With the morphine substitutes of synthetic origin (cf. group 3) it is quite different, as they are totally artificial substances.
One of the determining factors in the physician's choice of an analgesic is the centuries-old body of tradition underlying the use of opium therapy throughout the world. Opium and opium preparations are still officinal medicaments in the pharmacopoeias of all countries, and in many instances physicians, guided by clinical experience, choose opium extracts or compounds of pure alkaloids in preference to morphine itself or synthetic morphine substitutes.
A minimum of technical apparatus is required to manufacture analgesics from the poppy plant. In many countries with a rudimentary chemical industry the opium poppy is now and has been for hundreds of years a well-established crop. It is often an important element in the economy of a country, not merely as the raw material for the manufacture of opium and opium alkaloids, but frequently, and to a far greater extent, as the source of poppy seeds and poppy-seed oil. There is little likelihood that the cultivation of the poppy for these latter purposes will decline or disappear in thenear future. If these countries were to turn to imported synthetic analgesics instead of using their own available sources of supply, they would be following an unsound economic policy.
It is well known that the production of opium and the accompanying smuggling and abuse of the drug give rise to a series of social problems with serious and far-reaching implications. Various countries have attempted to cope with the evil by prohibiting the cultivation of the poppy plant, and to find an alternative solution to the analgesic problem partly through the import of opium and opium alkaloids and partly through the synthesis of morphine-like substances under strict national control. Obviously a policy of this kind may to some extent solve the problem as it affects a particular country, but not the international problem. As stated above, the cultivation of the poppy plant and the production of opium are so closely connected with the needs of national economies that a total prohibition of the cultivation of the opium poppy throughout the world at the present time would have serious economic consequences.
If there were a sudden change-over from the use of natural drugs to the use of synthetics, the normal outlets for opium would be suddenly reduced. Quantities of opium which could not be disposed of would sooner or later in all probability find their way into the illicit traffic, and the opium-producing countries would consequently be faced with a grave problem.
Today there are a great many known varieties and subspecies of the opium poppy, Papaver somniferum L. Papaveraceae. History shows that it is one of the world's oldest cultivated plants. This is also obvious from the fact that the plant is no longer found in a wild state. Most of the world's utility plants are more or less confined to a definite climate and within relatively narrow geographical limits. This is not the case with the opium poppy, which can be successfully grown in relatively large areas of the world with a high yield of opium alkaloids ([11] ). (cf. Fig. 1 and 2). It does not require any particular type of soil and reacts well to fertilizers. This is one of the main advantages in terms of agronomics, national economy and the available supply. As will be seen from the following diagram (Table I) several important industries all over the world are dependent on the opium poppy.
The opium poppy each year provides employment and a livelihood for a very large number of people in all its related industries and trades. Moreover, the world economy does not yet by any means exploit its potentialities to the full. The principal reason for this is to be found partly in governmental restrictions (cf. the Opium Poppy Control Act, 1942, which prohibits cultivation of the opium poppy in the United States without a licence), and partly in irrational operating methods dictated by tradition. The classical method of extracting opium (incising the capsule and gathering the dried latex) utilizes only a fraction of the plant's total alkaloidal content. The rest remains in the straw and the capsules which are mostly burnt or left to rot away. The method is based on almost two thousand years of tradition and is gradually being replaced by methods which require less human labour.
A large proportion of all the opium produced is used for the extraction of opium alkaloids. It immediately becomes obvious that when alkaloids are the end product, the intermediate stage of producing opium is an unnecessary expense.
Recognition of this fact is now becoming general, and the manufacture of opium alkaloids from poppy capsules and poppy straw is growing in certain countries, especially in eastern Europe. For example, 8 tons of morphine were manufactured from poppy straw in 1946, 17 tons in 1952, and 19 tons in 1953. In other words, in 1953 approximately one-quarter, in 1952 one-fifth and in 1946 one-sixth of all morphine manufactured was extracted from poppy straw ([20] ).
The future prospects of the poppy plant seem to be closely linked to the following conditions, to mention but a few : ([1] ) an expanded manufacture of opium alkaloids from the poppy plant itself (cf. above); ([2] ) the development of new varieties of the opium poppy; ([3] ) a steady and preferably increasing use of opium alkaloids. The last condition depends in part on the continued development of synthetic morphine substitutes and on whether science will succeed in manufacturing drugs free from the undesirable side-effects of morphine-primarily that of addiction. Research along this line is now in progress ([29] ).
The development of new varieties of the opium poppy should probably be planned with a dual purpose - (a) to develop varieties with a higher alkaloidal content than is found today in plants grown for both alkaloids and seeds;2(b) to develop plants with a low alkaloidal content or none at all, exclusively for seed production (cf. C. C. Fulton, p. 82).
The results obtained with the quinine tree Cinchona species demonstrated clearly that it is now possible to double the alkaloidal content of a plant. It would therefore not be unreasonable to assume that the alkaloidal content of the opium poppy can also be altered in one way or another. The methods formerly used by Dutch scientists in developing the quinine tree were primarily selection and crossing. In addition to these classical methods, there are today a number of new ones which have already produced noteworthy results in the cultivation of drug-producing plants. I refer particularly to polyploidys and the modern mutation methods using various rays (neutron rays in uranium piles, X-rays, ultra-violet rays and the like). The former method has been used particularly on higher types of plants, the latter on lower organisms, for example in the development of new strains of moulds and actinomycetes, etc., in the production of penicillin and other antibiotics.
Although intensive research has been carried out for centuries to ascertain the chemical composition of opium, much remains to be done before that goal is achieved. This point was also emphasized strongly in a recent article in the Bulletin on Narcotics ([5] ).
The pharmacopoeias require medicinal opium to be prepared with a fixed morphine content, usually approximately 10 percent. It should here be kept in mind that the various assay methods can give widely differing results ([1] , [14] ).
It is particularly important in this connexion to make clear the great significance of opium in modern therapy and the existing possibilities of replacing it with synthetic drugs. A study of the components of opium clearly shows it to be a product with a complex structure. Besides the active principle, morphine, a characteristic pharmacodynamic effect has also been observed in a number of the secondary alkaloids ([18] , [22] ). A synergistic or antagonistic relationship has also been found to exist between the various alkaloids ([18] ), and it has been possible to demonstrate that even the nitrogen free ballast components influence absorption from the intestine and thus the effectiveness of the drug. Accordingly, opium cannot yet be replaced by any single synthetic substance.
The other problem which still remains to be discussed is the role which opium plays in modern therapy and as a raw material for pharmaceutical preparations. Opium is included in all modem pharmacopoeias, and a large proportion of all the medicinal opium produced is used in the manufacture of galenical preparations such as Pulvis antasthmaticus, Pulvis Cynoglossi compositus, Pulvis Ipecacuanhae opiatus, Extractum Opii siccum, Tinctura Opii, Tinctura Opii Camphorata, Tinctura Opii Crocata, and the like. In this connexion also, the mixture of opium alkaloids should be mentioned. 2ff7e9595c