I THE OPIUM RESEARCH PROGRAMME
II. THE CANNABIS RESEARCH PROGRAMME
III. OTHER PROJECTS AND FUNCTIONS
Pages: 7 to 15
Creation Date: 1967/01/01
This Laboratory was originally established in order to carry out scientific research on opium. Its work has been subsequently broadened by the Commission on Narcotic Drugs to include research on cannabis, heroin and other substances under international control. The following article gives an account of the United Nations Laboratory and its work.
The Commission on Narcotic Drugs considered that it would be of great value in the fight against the illicit traffic in narcotic drugs if scientific methods could be developed for the determination of the geographic origin of opium.
Being an agricultural product, opium has physical and chemical characteristics which vary in certain respects according to the ecological conditions of the region where the poppy plant was grown and the opium harvested. It was believed that if the characteristics could be established for the opium from all regions where it was produced, this would provide a basis for the determination of the origin of seized opium. The United Nations opium research programme was founded by two resolutions of the Economic and Social Council [ 1] in 1948 and 1949 and the General Assembly of the United Nations, in adopting its resolutions 834(IX) of 14 December 1954, decided to establish the United Nations Narcotics Laboratory at Geneva. [ 2] The early history and development of the opium research programme has been described in a previous issue of the Bulletin (1966, Vol. XVIII, No. 1, 1)
The Division of Narcotic Drugs of the UN Secretariat, located in Geneva, carries out research on opium in its Laboratory. Sergei Koromyslov, (of the Laboratory's staff) explaining to Srinivasa Narayanan (India, foreground) a UN Technical Assistance Fellow, the spectrophotometric analysis of narcotic drugs at the Laboratory.
Special cards such as the one seen in this picture make possible the rapid retrieval of information on narcotic substances needed for the research at the Laboratory. .
In directing the activities within the opium research programme, the Council and the Commission have indicated the need for collaboration by Governments and a broad range of recommendations have been made in this respect. These include the provision of the basic research material (authenticated samples [ 8] and also samples from seizures) [ 4] the nomination of scientists to participate in the programme [ 5] , the communication of information to the Secretary-General [ 6] , and the provision of expert assistance. [ 7] The extent of this international collaboration is reflected in the very positive response of Governments to these recommendations
To facilitate the exchange of information, a special series of United Nations documents [ 11] is devoted to the assay, characteristics, composition and origin of opium and so far 144 papers (by the Secretariat and by collaborating scientists) have been issued in this series. As may be seen from a study of the documents in the ST/SOA/SER.K/.. series, many diverse methods were suggested (particularly in the early part of the programme) for the determination of the origin of opium. These methods involved many branches of chemistry - chromatography, electrophoresis, spectrography, activation analysis and also the quantitative determination of constituents of opium. However, none of these methods proved to be adequate - they were very lengthy, cumbersome and failed to give reproducible results.
The first positive achievements in the search for suitable methods for the determination of the origin of opium were realized with the development of the method of direct absorption spectrophotometry at the Institute for the Control of Drugs, Zagreb, Yugoslavia (December 1957), and the method of colour reactions at the United Nations Laboratory (January 1958). These methods fulfilled the important criteria (stressed by the Commission) [ 12] of being simple, rapid and easily reproducible, requiring small amounts of material and little specialized equipment. They could thus be applied in any reasonably equipped laboratory in the world. These methods were subsequently tested by collaborating scientists in several laboratories and the results of these analyses were found to be in very good agreement.
The determination of the origin of opium
Direct absorption spectrophotometry. In a study of the ultra-violet absorption spectra of very dilute aqueous extracts of Yugoslav opium, Grlic and Petricic [ 13] found significant differences between opium samples from Macedonia and those from certain northern regions of Yugoslavia. On the basis of these results, the research was extended in order to determine whether similar variations might be found in opium of different geographic origin. In a comprehensive study by Grlic, [ 14] the method of direct absorption spectrophotometry was applied to a large number of opium samples (from 17 countries) and it was found that this method offered considerable possibilities for the determination of the origin of opium.
Grlic's procedure was very simple and rapid and consisted of the preparation of an extract of the opium sample by triturating 25 mg in a small mortar for 1/2-I minute with a few drops of sodium acetate-hydrochloric acid buffer solution (pH 3.95). Thereafter, 5 ml of the same buffer solution were added and with stirring, after filtering, the extract was further diluted with the buffer solution until the extinction value at 250 m μwas between 0.6 and 0.9. The extinction values were then measured in a spectrophotometer within the range 250 to 320 m μusing cells a cm in width. Certain extinction quotients were then calculated (E/ 260/E 270, E 280/E 290 and E 300/E 310).
Although the extracts of opium showed certain common characteristics, Grlic found that there were appreciable differences in the absorption of samples from different regions. To explain these differences, it was assumed that the absorption curves of the opium extracts (although undoubtedly resulting from the large number of substances present in the extract) might for the greatest part be attributable to the additive absorption of the most important alkaloids and possibly to some organic acids bound to the alkaloids. This was confirmed by comparing the absorption spectra of the opium extracts with those for pure constituents of opium, as well as with the composition of corresponding samples as reported in the ST/SOA/SER. K/.. series. He made a detailed examination of the part played by the various constituents of opium in the formation of the absorption curves of the extracts and he concluded that the differences in the spectra were accounted for mainly by differences in the content of certain constituents (particularly thebaine, papaverine and meconic acid). The ratio between the amounts of thebaine and papaverine played a decisive part in the formation of the absorption curve of the extract - the variation in papaverine content seeming to have a greater effect than differences in the amount of thebaine present. The calculation of extinction quotients provided an approximate indication of the amounts of the substances present and also on their relationship with one another. For example, the quotient E 260/E 270 is in reverse relation to the ratio thebaine/ papaverine, while E 280/E 290 gives an idea of the amount of meconic acid present. Grlic analysed a larger number of samples and discussed the absorption characteristics of opium from different countries in detail.
With this method it was possible to separate samples of opium from different regions by plotting graphically two different quotients of extinction, Although good discrimination was obtained for many types of opium, particularly from South-East Asia, Japan, the Balkans and the Western hemisphere, it was sometimes difficult to clearly separate samples from some other countries (such as Indian, Iranian and Turkish samples one from another).
In order to obtain spectrophotometric data which might be affected by other relationships between the organic constituents, a further study l5 was made by Grlic in which the extraction procedure was changed and good results were obtained using normal sulfuric acid for this purpose.
The modified method consisted of triturating 25 mg. of opium in a mortar with a few drops of normal sulfuric for one minute, thereafter adding 10 ml of the same acid. After stirring for three minutes, the extract was filtered into a test tube which was then heated for 20 minutes in boiling water. After cooling, the absorption of the extract was measured in the region 450 to 540 m μ. The extracts were then diluted with normal sulfuric acid until at 250 m μa value of between 0.6 and 0.9 was reached. The absorption of the dilutions thus prepared were measured within the range 250 to 320 m μusing 1 cm cells.
According to this procedure, therefore, two sets of spectrophotometric readings were obtained - the measurements of the undiluted extracts in the visible region of the spectrum and the measurements of the diluted extracts in the ultraviolet region. Calculations were made of the quotients E 250/E 260, E 260/E 270, E 290/E 300 and E 480/E 500.
In the visible region, the differences observed in the shapes of the curves were due for the greatest part to differences in the content of porphyroxine-meconidine of the samples examined - this alkaloid giving a characteristic red colour on heating with mineral acids. The ultra-violet absorption spectra of the opium extracts were compared with those for pure constituents of opium treated in a similar way. It was found that the most marked changes were attributable to the thebaine which was converted to thebenine after heating with acid.
The extinction quotients obtained using this procedure were found to be characteristic for the opium samples from different regions - including those which could not be differentiated by the earlier method. It was recommended that both the buffer and acid procedures should be used.
Further research at the Institute for the Control of Drugs, Zagreb, by T. Bian-Fišter l6 confirmed the usefulness of the method of direct absorption spectrophotometry and a paper by V. Kuševic [ 17] indicated its importance as a method for the determination of the origin of opium.
The Secretariat has adopted this method, but in order to use it in conjunction with the method of colour reactions, the extraction procedure has been modified. [ 18] A quantity of 0.25 g of opium is triturated with small amounts of glacial acetic acid until 2.5 ml have been added, the trituration being continued until a homogeneous paste is obtained. 25 ml of water are added with constant stirring and the extract is filtered. Next 5 ml of the filtrate are pipetted into a 25 ml flask which is made up to the mark with normal sulfuric acid. The flask is heated in a boiling water bath for 20 minutes and, after cooling, the extinction of the solution is measured at 480 and 500 m μ. The solution is then diluted with normal sulfuric acid until at 250 m μan extinction value of between 0.5 and 1.0 is reached. The extinction values are then measured within the range 250 and 320 m μand the quotients are calculated.
In spite of the different procedures used for the preparation of the extracts, the extinction quotients found were generally in good agreement with those reported in document ST/SOA/SER.K/75 - although for certain quotients slight, but constant differences were noted. However, the results obtained using glacial acetic acid were also shown to be very characteristic for opium from different regions. A large number of authenticated samples were examined and the results are reported in the ST/SOA/SER.K/.. series. [ 19]
The buffer procedure described in document ST/SOA/ SER.K/54 by Grlic is also used by the Secretariat in a slightly modified form, [ 20] the extract being prepared with glacial acetic acid and subsequently diluted with a buffer solution of pH 4. The extinction values are measured in the region 250 to 320 m μand the quotients calculated. The results obtained for the authenticated samples analysed by this procedure are given in the ST/SOA/SER.K/.. series. [ 21]
Colour reactions. In the pharmacopoeiae, simple qualitative colour tests have been used as a means of broadly indicating the region of origin of certain plant products (such as aloes), and the Secretariat investigated the possibility of applying this principle to the problem of the determination of the origin of opium. A large number of colour reactions for the various constituents of opium were tested and the four most promising ones were selected for further study. These were the reactions with hydrochloric acid, ferric sulfate, phosphoric acid and formalin and bromine. (The reaction with formalin and bromine was subsequently replaced by the reaction with sodium nitrite and ammonium hydroxide, which was found to give more reproducible results). A preliminary report [ 22] indicated the usefulness of these reactions in general and it seemed that a method based on colour reactions would fulfil the criteria stressed by the Commission of being simple, rapid and easily reproducible. Further research was carried out [ 23] - the optimum conditions for each reaction were established and a large number of authenticated samples were analysed.
The method is very simple. An extract of opium is prepared with glacial acetic acid as described above and subsequently diluted with water and filtered. The filtrate is used for each of the reactions.
Heating extracts of opium with mineral acids produces a red colour due to the alkaloid porphyroxine-meconidine in the opium and the use of this reaction was reported in several papers in the ST/SOA/SER.K/.. series. [ 24] In the procedure used by the United Nations Laboratory, 5 ml of the filtrate are heated in a boiling waterbath with 20 ml hydrochloric acid (0. 2N). After cooling and subsequent dilution to 50 ml with the same acid, the extinction of the solution is measured at 480 and 510 mμ. With this reaction, the extinction values varied considerably for opium from different countries, high values being obtained for Japanese opium and very low values for opium from Iran, corresponding to the data in the literature for the comparative prophyroxine-meconidine values for opium from these countries. [ 25] It was found that opium from Afghanistan, China, Korea and Turkey showed relatively low values, while the values for samples from South-East Asia and Yugoslavia fell within the intermediate range. Indian opium varied from intermediate to high.
Ferric salts yield a red colour with the meconic acid in opium and the use of this reaction as a basis for the determination of meconic acid has been reported by Witte. [ 26] To minimise possible interference from morphine and other phenolic alkaloids (which react with ferric sulfate when the pH is nearly neutral) the Secretariat uses a buffer solution. For this reaction, 1 ml of the filtrate is treated with 5 ml ferric sulfate solution 0.5 % and diluted to 25 ml with a buffer solution of pH 2.0 Extinction measurements are made at 450 and 480 mμ. Low values were obtained for opium from Turkey and intermediate values for Iranian and Yugoslav opium. Indian samples generally gave high values.
In the reaction with phosphoric acid, the thebaine produces a strong yellow colour. For this test, 1 ml of filtrate was treated with syrupy phosphoric acid to give a volume of 25 ml and the solution was well shaken. After standing for two hours in order to allow the colour to develop fully, the extinction was measured at 350 and 390 mμ. As was to be expected, this reaction showed high values for opium rich in thebaine (from Iran and South-East Asia) whereas rather low values were found for opium from most other regions.
When an extract of opium is treated with sodium nitrite and ammonium hydroxide under certain conditions a strong reddish brown colour is produced due principally to the morphine in the opium, and the Secretariat has adapted this reaction, the details of which are given in documents ST/SOA/SER.K/104 and K. 116. [ 27] To 1 ml of the filtrate are added 7 ml 15% acetic acid, followed by 1 ml 1% sodium nitrite solution. After cooling and standing for 15 minutes 10 ml 10% ammonium hydroxide solution are added, the solution subsequently being diluted to 50 ml with distilled water. After standing for 30 minutes the extinction is measured at 400, 410 and 440 mμ. The values were found to be characteristic for opium from certain regions.
Using these four reactions, the Secretariat has analysed the authenticated samples available. [ 28] Although each reaction is specific for one of the constituents of opium, it is obvious that other constituents participate to a lesser degree in the formation of the coloured products. This however, is not significant as each reaction has proved its diagnostic value in the determination of the origin of opium. Ranges of extinction values have been established for opium from different countries and it was found that important information could be obtained by plotting graphically the extinction values obtained from two different reactions.
Application of methods. In determining the origin of opium seized in the illicit traffic, the sample is first examined macroscopically and microscopically. [ 29] The morphine content is determined in order to prove that the substance under investigation is opium. The sample is then analyzed by the methods of direct absorption spectrophotometry and colour reactions and the data obtained are compared with the data for all the authenticated samples analyzed by the United Nations Laboratory by means of a punched card systems which makes rapid and accurate comparisons possible.
The Commission has always been concerned that the abuse of cannabis constitutes a serious problem in many countries, and in 1954, at its ninth session, it expressed interest in tests for the identification of cannabis and also in research directed towards the determination of the active principle or principles which it contained. Accordingly, the Secretariat was authorized, in appropriate cases, to seek information from Governments on work carried out in this field in their respective countries. [ 30] Information was provided by Governments [ 31] for consideration by the Commission which, at its twelfth session, invited all Governments having the necessary facilities to promote such research. [ 32] The Commission subsequently felt that it would be desirable to co-ordinate at the international level the research being carried out on cannabis and, at its thirteenth session requested [ 33] that consideration should be given to means by which this co-ordination could be achieved. It also requested that the Laboratory should carry out a preliminary study on methods for the identification of cannabis. The following year the Commission established the cannabis research programme. [ 34] The primary objective was the improvement of methods for the identification of cannabis as the Commission felt that this would be of value in the fight against the illicit traffic. Governments were invited to make available the results of research work carried out in their countries and the Secretariat was requested to assist in co-ordinating the work done at the national level. For this purpose, the Secretariat was to organize the exchange of information and the distribution of cannabis samples and also to arrange for studies to be carried out on this subject. It was, in addition, to investigate methods for the identification of cannabis.
Governments indicated their interest in the cannabis programme by nominating scientists to collaborate. in the work and by providing the research material. The Laboratory now has a wide range of cannabis samples from many parts of the world, [ 35] which are available to all scientists participating in the programme.
The UN Cannabis reference sample
Until recently, one of the difficulties in research in this field was the fact that researchers worked on cannabis from different parts of the world and it was therefore not possible for comparisons to be made of the results obtained - because the amount and potency of the resin varies according to the ecological conditions of the region where the cannabis was grown. The resin of cannabis grown in tropical or semi-tropical regions has greater pharmacological effects than the resin from cannabis cultivated in temperate zones. At the suggestion therefore of Professor Joachimoglu of Athens, the Laboratory prepared a "reference" sample of cannabis in 1965. This was made by taking quantities of all the samples in the collection of the United Nations and mixing them very throroughly to ensure complete homogenity. The cannabis was then packed under nitrogen in air-tight packets. These have been sent on request to several collaborating scientists. It is hoped that the reference sample will be of value in both pharmacological and chemical investigations by making it possible to compare the composition and activity of cannabis from different parts of the world and also to compare results obtained by various methods.
A special series of United Nations documents is devoted to the cannabis research programme [ 36] and the results obtained by the Secretariat and by collaborating scientists are presented in this series. Up to the present time, fourteen such papers have been issued. Articles on scientific research on cannabis are also published in the Bulletin on Narcotics.
The Secretariat began its research by examining the specificity of certain chemical reactions used for the identification of cannabis. [ 37] The tests most commonly used for this purpose (the Beam, Ghamravy and Duquénois-Negm reactions) were applied to the samples of cannabis which were available at the time and also to 120 other plant species. It was found that, while all the cannabis samples gave a strongly positive Duquénois-Negm test, the results varied from sample to sample with the Beam and Ghamravy reactions. Some other plant species showed certain tendencies to react with the tests for cannabis - particularly in the case of the Ghamravy reaction - and these were mostly plants containing volatile oils. [ 38] From the results obtained, conclusions were drawn concerning the specificity, sensitivity and usefulness of these three tests for the identification of cannabis.
A study was also made of the possibility of identifying cannabis by means of ultra-violet absorption spectrophotometry. [ 39] Ethanolic extracts of cannabis resin showed selective absorption spectra, but the shape of the curves and the position of the absorption maxima varied considerably. These differences were attributed to a process of gradual conversion of cannabidiolic acid to other substances and this process was called "ripening". Samples showing two absorption maxima (one at about 260-270 mμ and one at about 304 mμ) were supposed to contain a high percentage of cannabidiolic acid and were classified as being of the "unripe" type; in the samples showing only one maximum (at about 270-280 mμ) the more thermostable products of the decarboxylation of the acid seemed to predominate and these were classified as being of the "ripe" type. Some samples were found to be of an intermediate type. A study of the absorption characteristics of cannabis from different regions indicated that the "ripening" was more advanced in samples from tropical regions. This process also occurred during storage. Certain other plant species showed absorption characteristics similar to those of cannabis. It was concluded that ultra-violet spectrophotometry was of limited value for identification purposes because the absorption characteristics of the cannabis extracts were not specific enough. It was suggested, however, that information on the chemical composition of cannabis resin might be provided by ultra-violet spectrophotometry.
In collaboration with Professor Zd. Krejc, [ 40] the United Nations Laboratory has carried out research on the application of thin-layer chromatography to the analysis of cannabis. 4l Extracts of cannabis samples were prepared with petroleum ether and with 90% ethyl alcohol and the resin fraction (containing a mixture of the acid and phenolic components) was isolated by means of aqueous sodium hydroxide solution. Results were reported for cannabis of different origins. The reference sample was analysed in a similar way and, in addition, the relative proportions of the substances of acid and phenolic character were determined. The complete extracts and also the isolated fractions were subjected to thin-layer chromatography, using a mixture of anhydrous benzene and anhydrous ethyl alcohol (95:5) as the solvent phase, and 2,6-dibromoquinone chlorimide and 2% sodium carbonate solution as the developing agents. The chromatographs were compared with those of chemically pure substances isolated from cannabis by research workers of the Olomouc Faculty of Medicine and of the University of Bonn. [ 42] It was established that the tetrahydrocannabinol and the cannabidiol remained intact in the alcoholic residue after the separation of the acid part of the extract.
Very important contributions to the cannabis research programme have been made by collaborating scientists. Farmilo of Canada presented a review of results on the chemical analysis of cannabis, [ 43] including the isolation and assay of the phenolic constituents, colour tests and also a study of the essential oil of cannabis. The forensic aspects of the identification of cannabis were also discussed. In a later paper, [ 44] Farmilo et al. reported research carried out in order to elucidate the possible biogenetic pathways for the production of cannabinols in the plant. Based on scientific investigations (by means of paper and gas chromatography and colour tests) of the chemical composition of cannabis of different origins a theoretical biogenetic scheme was presented.
In Yugoslavia, Grlic made several studies on cannabis including research on its antibiotic activity [ 45] and on the possibility of distinguishing various types of cannabis resin by means of a simple test with ferric chloride solution. [ 46] He also examined the infra-red spectra of cannabis resin [ 47] and carried out research on the extent to which the characteristics of cannabis might undergo modifications if grown under changed environmental conditions and seeds from cannabis of various origins were cultivated experimentally at the Institute for the Control of Drugs at Zagreb. [ 48]
In a paper on cannabis cultivated for industrial purposes in Hungary, Fritz et al. [ 49] found that this contained only very small amounts of pharmacologically active substances. Lerner, of the United States of America, reported a method for determining simultaneously the cannabidiolic acid, cannabidiol, tetrahydrocannabinol and cannabinol in cannabis by means of gas chromatography. [ 50] Research on the isolation and structure of cannabinolic, cannabidiolic and cannabigerolic acids was carried out by Mechoulam and Gaoni of Israel. [ 51] The methods used for the identification of cannabis
by the authorities in the United States of America were also reported in the ST/SOA/SER.S/.. series. [ 52]
In the Commission on Narcotic Drugs, it has been suggested that it would be useful to have suitable tests for the detection of cannabis users - particularly in the case of automobile accidents. [ 53] Research on the identification of cannabis in body fluids is being carried out in collaborating laboratories.
Research on heroin.
The Laboratory was also asked to examine the possibility of determining the origin of heroin. [ 54] Since heroin is a manufactured product, its characteristics are not related to ecological factors and therefore, the problem of the determination of the geographic origin of seizures is considerably more complex for heroin than for opium. However, illicitly-made heroin is often incompletely acetylated and it always contains impurities and diluents. There were indications that it might be possible to compare seizures of heroin by determining the degree of acetylation and the nature and the amount of the impurities present. It was thought that being able to relate heroin seized in different places might provide useful information for enforcement officers. Research along these lines was carried out in Canada and in the United States of America and the Secretariat prepared a preliminary report [ 55] on this subject which was based on information received from collaborating scientists in these countries. Research on the determination of the origin of heroin has, however, been suspended by the Laboratory, in view of the higher priority assigned to other projects.
The Laboratory has been requested to carry out research on methods for the identification of natural and synthetic narcotic drugs [ 56] and also on other substances which engender dependence, [ 57] (such as hallucinogens and sedative and stimulant drugs).
Lists of drugs.
In pursuance of resolution 49 (IV) of the Economic and Social council which provided, inter alia, that the Secretary-General should undertake "the revision of the list of narcotic drugs falling within the scope of the various conventions", two reference documents on narcotic drugs are regularly prepared by the Laboratory.
The "List of narcotic drugs under international control" is issued annually and gives, for each drug, the proposed international non-proprietary name, the chemical description, the treaty whereby the substance was brought under control and an indication of whether the drug is a natural substance, or derived from opium or the coca leaf, or a synthetic product.
The "Multilingual List of Narcotic Drugs under International Control" is issued from time to time and gives the names, synonyms, chemical and structural formulae for narcotic drugs not only in the working languages, but also in many other languages and non-Latin alphabets. Other relevant information is also provided such as the empirical formula, molecular weight and percentage of anhydrous base for each drug and its salts. Two editions of the Multilingual List have been issued [ 58] and, at the request of the Commission, the Laboratory is preparing the third edition, which it is hoped to publish in 1968.
Training provided by the Laboratory.
Another important function of the Laboratory is the provision of training within the United Nations Development Programme (formerly known as the Technical Assistance Programme). Under this scheme, fellowships are awarded to chemists - usually from developing countries - working in the field of narcotic drugs, who have been recommended by their Governments for study at the United Nations Laboratory. At first, such awards were made for the purpose of training in methods for the determination of the origin of opium but, as suggested by the Commission on Narcotic Drugs, [ 59] the training is now given on a wider basis, with special reference to modern techniques and instrumentation used in the study of narcotics and including the study of analytical methods for cannabis, opium and other drugs as well as general laboratory organization. Since 1958, seventeen fellowships have been awarded and chemists from China, Greece, Hungary, India, Iran, Madagascar, Senegal, Spain, Thailand, Turkey and Yugoslavia have received training at the Laboratory. The fellowships are generally awarded for periods of six months, and may in some cases be extended if necessary. While the fellows are at the Laboratory, arrangements are made wherever possible for them to visit various laboratories and scientific institutions within reasonable distance of Geneva.
Governments have expressed their appreciation of the training provided and the importance of these fellowships is clearly indicated in the reports made by the fellows.
The Laboratory has a unique collection of scientific literature on narcotic drugs, consisting of about 30,000 documents and reprints. The classification of the material has been done in such a way as to facilitate rapid retrieval of information, and the system in use has proved to be very effective. This is of great value, not only for the research of the Laboratory, but also for the provision of advisory services of a scientific and technical nature to the Division of Narcotic Drugs and other United Nations bodies, as well as to collaborating scientists and others.
There is also collaboration with the World Health Organization on certain projects. In 1953, a study was undertaken jointly with WHO in order to throw light on some basic problems arising from the development of synthetic narcotic drugs. The results of this study appeared in a series of reports entitled "Synthetic substances with morphine-like effect". [ 60] The Laboratory has also carried out experiments on the convertibility of new drugs to substances under international control. In 1964, the Laboratory provided the WHO Expert Committee on the International Pharmacopoeia with comparative data for the morphine content of opium samples analyzed by different methods. For the subsequent collaborative study carried out by WHO in order to evaluate methods for the determination of morphine, the Laboratory prepared the reference samples for analysis by chemists in various countries. Training facilities have also been provided at the United Nations Laboratory for chemists awarded Technical Assistance fellowships by WHO.
The United Nations Laboratory and national scientists collaborating in the research programmes have made important contributions to the solving of scientific and technical problems in the field of narcotic drugs. The results obtained in the research on opium and cannabis have proved that such questions can most effectively be dealt with on an international basis.
The pattern of drug abuse has changed considerably in recent years. There is a widespread increase in the abuse of narcotic drugs (and in the illicit traffic therein) and also in the number of drugs which are abused. A serious problem has also developed in many countries in connexion with the abuse of barbiturates, amphetamines, tranquillizers and hallucinogens, which are not at present under international control. The diversity of drugs which are abused at present will necessitate extensive research on methods for their identification - not only in pharmaceutical preparations but also in body fluids. There is no doubt that the experience gained in the earlier research programmes will be of great value to the Laboratory and its collaborating scientists in solving these new problems.1
Resolutions 159 II C (VII) and 246 F (IX).2
The equipping of the Laboratory was facilitated by a financial grant from the Cantonal Authorities of Geneva.3
The fundamental basis for all the research on opium is the collection of authenticated samples of the United Nations Laboratory. Governments have provided and are continuing to provide the samples needed. [ 8] Up to the present time, 779 such samples have been received (some of these samples consist of more than one part and the total is therefore over 900 if this is taken into consideration). These samples are used by the Secretariat for its research and are also sent on request to collaborating scientists. The United Nations Laboratory has therefore a wide range of authenticated samples, but further samples are still needed particularly from regions directly affected by the illicit traffic such as the Middle East and South-East Asia.
In addition, non-authenticated samples and samples of seized opium for research purposes have also been furnished [ 9] and many Governments have submitted seizures samples for the determination of origin. l0
Governments have indicated their interest in the research by nominating scientists to participate in the programme. Eighty-four scientists (from 29 countries) have been so nominated, although the number actively participating is somewhat smaller. These scientists carry out research on a voluntary basis according to their own special interests and to the facilities which are available to them. Collaborating scientists have made very important contributions to the opium programme. The United Nations Laboratory acts as the centre of the research and assists in co-ordinating the work done at the national level.
An authenticated sample is a sample which has been guaranteed by the government of the country of origin as opium produced in that country.4
Council resolutions 159 II C (VII), 436 F (XIV), 548 D (XVIII); Commission resolutions B.I. (X) 1955, II, III (XII) 1957, V (XIII) 1958, 6 (XIV) 1959, 3 (XVII) 1962.5
Council resolution 159 II C (VII), Commission resolution II, III (XII) 1957.6
Council resolution 159 II C (VII).7
Council resolutions 447 (XV) and 626 H (XXII).8
Since 1948, the following Governments have furnished the United Nations with authenticated samples-the number of samples provided being indicated in parentheses: Afghanistan (4), Burma (7), China (1), Greece (1), India (567), Iran (32), Japan (22), Korea (4), Laos (5), Mexico (5), Nepal (1), Pakistan (13), Thailand (2), Turkey (87), Union of Soviet Socialist Republics (16), Viet-Nam (1), Yugoslavia (11). It should be noted that, whereas the greater majority of these samples are from the legal production, some authenticated samples have also been provided from illicit cultivation.9
Such samples have been received from Australia, Bahrain, Burma, Ecuador, the Federal Republic of Germany, Iran, Israel, Pakistan, Portugal, Singapore and the United States of America.10
Seizure samples for the determination of origin have been received from Aden, Australia, Cambodia, France, the Federal Republic of Germany, Hong Kong, India, Iran, Iraq, Italy, Jordan, Lebanon, the Netherlands Antilles, New Zealand, Pakistan, Singapore, Sudan, Sweden, Syria, Thailand, the United Arab Republic, the United Kingdom and the United States of America.11
The ST/SOA/SER.K/.. series.12
Commission resolutions 5 (XIII) 1958 and 6 (XIV) 1959.13
ST/SOA/SER.K/88, K/93 and K/94.17
ST/SOA/SER.K/4, K/8, K/10, K/14, K/19, K/65, K/71, K/75, K/76, K/77, K/80; also documents E/CN.7/195 and E/CN.7/ 207.25
E/CN.7/195, E/CN.7/207, ST/SOA/SER.K/4, K/8; Asahina, H., (1954) Bull. Nat'l Hyg. Lab., 72, 73; Asahina, H., (1955) Bull. Nat'l Hyg. Lab., 73, 63.26
The preliminary study of this reaction was carried out by V.S. Ramanathan (Chemical Examiner, Central Revenues Chemical Service, Ministry of Finance, New Delhi, India) while at the United Nations Laboratory on a Technical Assistance fellowship.28
ST/SOA/SER. K/115, K/l16, K/130, K/140.29
Although not of itself a method for the determination of origin, microscopic examination can sometimes provide important confirmatory evidence - see document ST/SOA/SER.K/104.30
Report, ninth session, para. 105.31
E/CN.7/298 and Adds. 1-6.32
Resolution IV(XII) 1957.33
Resolution VI(XIII) 1958.34
Resolution 8 (XIV) 1959.35
Cannabis samples have been received from Bahrain, Brazil, Canada, Cyprus, Denmark, the Federal Republic of Germany, Ghana, Greece, India, Iraq, Lebanon, Madagascar, Morocco, Nigeria, South Africa, Spain, Sweden, Switzerland, the United Kingdom and Venezuela. Some of these samples were of cannabis grown for experimental purposes or from normal production, while others were from seizures.36
The ST/SOA/SER.S/.. series.37
The Secretariat later studied some of the pure constituents of plants including constituents of the volatile oils of aromatic plants; these were tested with the three reactions for cannabis and the results are reported in document ST/SOA/SER.S/5.39
Director of the Institute of Hygiene and Epidemiology at the Faculty of Medicine, Palacky University, Olomouc, Czechoslovakia.41
The crystalline cannabinol and the tetrahydrocannabinol were kindly supplied by Drs. Sieper and Claussen respectively of the University of Bonn and the cannabidiolic acid, the acetyl ester of cannabidiolic acid, the transcinnamic acid and n-nonacosane by Professor Šantavi of Palacky, University, Olomouc.43
Commission report, eighteenth session, para. 224.54
Commission report, nineteenth session, paras. 184 and 186.55
Commission report, eighteenth session, para. 180.57
Commission report, twenty-first session, para. 332.58
E/CN.7/341 (1958); E/CN.7/436 (1963).59
Braenden, O. J. & Wolff, P. O. (1954) Bull. Wld. Hlth. Org., 10, 1003. Braenden, O. J., Eddy, N. B. & Halbach, H. (1955) Bull. Wld. Hlth. Org. 13, 937. Eddy, N. B., Halbach, H. & Braenden, O. J. (1956) Bull. Wld. Hlth. Org. 14, 353. Eddy, N.B., Halbach, H. & Braenden, O. J. (1957) Bull. Wld. Hlth. Org. 17, 569.