World Health Organization Expert Committee on Addiction-producing Drugs: Tenth Report
Pages: 47 to 49
Creation Date: 1960/01/01
The Secretary summarized the report of the fourteenth session of the Commission on Narcotic Drugs of the Economic and Social Council; [ 2] the relevant resolutions of the Economic and Social Council; [ 2] and the latest reports of the Permanent Central Opium Board [ 3] and the Drug Supervisory Body. [ 3] Among the items of interest, note was taken of the difficulties encountered in the international control system as a result of delays by some governments in subjecting new narcotic drugs to national control. The placing of a drug under national control may be the first indication to a medical practitioner that it is addiction-producing; and when a drug comes rapidly into favour for medicinal use, as was the case with dextromoramide, any delay in the recognition of its addicting potentialities enormously accentuates the public health dangers.
In connexion with the abuse of drugs, the Committee noted that statistics on addicts in different countries were based on different criteria. It would be desirable for some common basis to be found for compiling such statistics; and it might be helpful if information on addicts who come into conflict with narcotic laws or become known in some other way could be supplemented by statistics on the number of people for whom particular drugs are prescribed on a long-term basis.
The Committee noted that some of the drugs falling under international control had never been placed on the market. In some instances it was known that producers decided not to proceed with the commercial development of a drug when a decision had been reached that it was addiction-producing. The number of such drugs may increase in the future, and the inclusion of so many drugs may result in the list of addiction-producing drugs becoming excessively long, which may be an administrative embarrassment. It would be helpful for certain purposes if the lists of controlled drugs 4 5 could be complemented by an up-to-date list of drugs actually on the market, arranged according to their international non-proprietary or common names, for the practical use of control authorities. The list should also indicate the name under which each substance is sold, and the meaning of each name in terms of base, salt or preparation. Such a list would supplement the "Multilingual list of narcotic drugs under international control " [ 6] until revision is possible.
The Committee noted the increasing interest in mass campaigns against opium addiction, and would point out that, for the treatment of such addicts, simple methods of withdrawal are available, which have proved to be successful under various circumstances.
Addiction Liability, Chemical Structure, and Control
In 1949, the Commission on Narcotic Drugs of the Economic and Social Council, [ 7] considering that varying degrees of control should be applied to different classes of substances, requested the Expert Committee on Addiction-producing Drugs " to furnish the Commission, at its fifth session, with definitions of the terms' drug addiction ', ' addiction-forming drugs ', 'habit-forming drugs' and 'fundamental structure of an addiction-forming drug', and to illustrate such definitions by references to appropriate drugs ".
The Committee formulated draft definitions of drug addiction and habituation in the report on its second session, [ 8] and attempted to clarify the distinction in its third report. [ 9] Revised definitions were approved in its seventh report. [ 10]
4 Annex to the Permanent Central Opium Board's statistical form.
5 List of drugs under international control, published annually by the United Nations Division of Narcotic Drugs.
These definitions have had some acceptance and have served a useful purpose. However, in order to make them applicable to the various substances under international control, they had to include heterogeneous criteria, and these criteria are difficult to interpret. Even if the definitions were re-written to be specifically descriptive of the various qualitative types of addiction, all of which involve drug-induced behavioural disturbances, some difficulties would still remain regarding their applicability to control. The fundamental criterion for control is the extent to which these drug-induced behavioural disturbances are a risk to the community.
With further reference to the Commission's request, the Expert Committee, in the report on its second session, [ 11] said that, in the present state of our knowledge, it was not possible to say what part of the molecule of a drug was responsible for its addiction properties, but that it was known that certain drugs, having, in the main, a common structure, produced in some degree a similar addiction. At that time, examples of common structure with relation to addiction-production included the groups of which morphine, pethidine, and methadone were members. The Committee emphasized that this list was not complete, and that probably new compounds of different structure would be developed which were also addiction-producing. This has since been realized, for example, in dimenoxadol and certain benzimidazole derivatives.
In this connexion, it was said only a few years ago [ 12] that certain chemical characteristics are common to morphine-like analgesic and addiction-producing drugs. Since then, structures have become known which are potent in both respects, but which lack one or other of the common chemical characteristics. [ 13]
There is, in addition, some evidence that analgesic effect and addiction liability can be modified in one substance in opposite directions - i.e., substances have been synthesized which combine strong morphine-like analgesia with a lowered addiction liability. Substances are known which are more potent than morphine in analgesic effect, in the production of morphine-like subjective effects, in the suppression of abstinence phenomena, and in the prevention of such phenomena by substitution in morphine-addicted individuals. On these accounts alone, these substances would be rated more likely to abuse, and hence perhaps more dangerous than morphine. On the other hand, the abrupt withdrawal of these same substances (after substitution or direct addiction) results in a relatively mild abstinence syndrome, the only available measure of physical dependence. This evidence would indicate less liability to the development of physical dependence under conditions of prolonged administration.
It should be clear from the foregoing that the primary consideration, in deciding whether a drug should be subject to control and to what degree, is liability to abuse, resulting in risk to the community.
No definition, however descriptive, can be a complete guide to what should be controlled. Similarly, in the light of our present knowledge, chemical structure per se cannot be the sole criterion. There are certain chemical groups of drugs - e.g., the morphine, pethidine and methadone groups - one or more members of which have been shown to be addicting. Within such groups, closely similar structures must be suspect unless and until there is convincing evidence that they are not addiction-producing. In the meantime, control measures of a provisional nature are justified.
Diverse structures are being developed which have a morphine-like action with varying degrees of addiction liability. In every case, an assessment will have to be made of the degree of risk to the community, based on liability to abuse, and consideration will have to be given to therapeutic advantages. Then, finally, it will be possible for the degree of control commensurate with the risk to the community to be established by the World Health Organization.
Research in the Field of Drug Addiction
The Committee has repeatedly stressed the need for research along various lines in the field of drug addiction. In order to contribute adequately to the World Health Organization's functions under the various international conventions controlling narcotic drugs, the Committee must have at its disposal the results of basic and applied research in this field. The Committee has had to deal repeatedly with notifications without adequate information so that decisions have had to be deferred. At present, the Committee's work depends in large measure upon the receipt of information respecting work carried out at the Addiction Research Center (United States of America), and the Department of Pharmacology of the University of Michigan (United States of America), and on the results of controlled clinical investigation, many of which are funnelled through the Committee on Drug Addiction and Narcotics of the National Research Council (United States of America). Because of their heavy workloads, these institutions, even though they have endeavoured to give priority to specific requests from the Expert Committee, have not always been in a position to furnish the Committee with the necessary information in time for it to take action as early as desirable. Thus, the preventive character of the international control measures has been hampered. In order to ameliorate this situation, means should be found to expand research activities, as outlined above, and to extend them to other parts of the world.
Moreover, the Committee emphasized again that drug addiction affects large numbers of people in many areas of the world and is, therefore, an international public health problem of great magnitude. Research in this field has not had the degree of support commensurate with its importance. The Committee therefore strongly urged that research on narcotic action and other aspects of drug addiction should be strengthened and expanded. A few of the topics on which work could profitably be enhanced or initiated include:
Basic investigations of the mechanisms of action of addicting drugs and of drug addiction, utilizing techniques from all pertinent fields, such as pharmacology, experimental psychology, biochemistry, neurophysiology;
Epidemiology of drug addiction [ 14] (almost nothing has been done on this subject);
Controlled evaluations of programmes for treatment of drug addiction;
Development and calibration of methods for assessing addiction liability in animals;
Clinical evaluations of new drugs with respect to analgesic action, liability to cause side actions, and development of tolerance and physical dependence under conditions of clinical use;
Cumulation, codification and making available information on all aspects of drug addiction. An initial effort in this direction is represented by the work on "coded information on narcotics ". [ 15]
Carriage of Narcotic Drugs in First-Aid Kits of Aircraft Engaged in International Flight
The Committee's attention was drawn to a report [ 16] on the principles under which opiates or similar drugs might be used and carried in first-aid kits on board aircraft engaged in international flight, and on the application of efficient safeguards against abuse. The Committee concurred with all the conclusions and suggestions, except that it was of the opinion that morphine should not be given orally, and that the dose to be used might be reconsidered with a view to its reduction to 10 mg per ampoule. The Committee was also of the opinion that a morphine antagonist (e.g., nalorphine) should be carried, and that instruction on the indications which would warrant its use should be included in the training of authorized personnel.
Proposed Single Convention on Narcotic Drugs
Schedules and Scope of Control
The Committee was pleased to note that in drafting the Single Convention on Narcotic Drugs, [ 17] attention had been given to the principle referred to in the present report (paragraph entitled "Control", page 4) - i.e., that the essential criterion for the establishment and degree of control is risk to the community. This consideration appears to be reflected in the implementation of schedules I to IV, where variations in the degree of the control measures applied are related to differences in the risk involved with various substances.
The Committee would reiterate the opinion expressed in its ninth report on the seriousness of placing a substance in schedule IV with its absolute prohibition as now drafted. When liability to abuse is great, lack of medical need and obsolescence for other purpose could justify prohibition. In any case, very careful balancing of risks against possible therapeutic advantage should be undertaken, restricting as little as possible the availability of medicaments to physicians. Where a drug appeared to represent a particularly high danger to the community, as in the case of diacetylmorphine (heroin), relevant recommendations to prohibit or restrict legitimate use could continue to be made by the international organs concerned; but decisions thereupon should not be mandatory.
In this connexion, the Committee would draw attention to the repeated references to diacetylmorphine in its reports. [ 19] [ 20] [ 21] The Committee reaffirmed its stand on the replaceability of this dangerous addicting agent; and the marked decrease in production of the drug, together with the small number of countries not prepared to suppress its use, indicates that the recommendation of the Commission on Narcotic Drugs of the United Nations Economic and Social Coucil [ 22] urging its prohibition had been very largely followed.001p047
1 World Health Organization, Technical Report Series (1960), No. 188.002p047
2 See Bulletin on Narcotics, vol. XI, No. 4.003p047
3 See Bulletin on Narcotics, vol. XII, No. 1.006p047
6 United Nations (1958) multilingual list of narcotic drugs under international control (document E/CN.7/341).007p047
7 United Nations Commission on Narcotic Drugs, Report of the Fourth Session (16 May-3 June 1949) - (Economic and Social Council, Official Records: ninth session. Supplement No. 9), Lake Success, New York (document E/1361-E/CN.7/186, p. 61).008p047
8 Wld. Hlth. Org. techn.Rep.Ser., 1950, 21, 6 (section 6).009p048
9 Wld. Hlth.Org. techn.Rep.Ser., 1952, 57, 9 (section 6.1).010p048
10 Wld. Hlth.Org. techn.Rep.Ser., 1957, 116, 9 (section 8).011p048
11 Wld. Hlth.Org. techn.Rep.Ser., 1950, 21, 7 (section 6.4).012p048
12 Eddy, N.B., Halbach, H. & Braenden, O.J. (1956), Bull.Wld. Hlth. Org. 14, 353.013p048
13 Eddy, N. B., J.Soc.chem.Ind. (Lond.) (in press).014p049
14 World Health Organization, Study Group on the Treatment and Care of Drug Addicts (1957), Wld.Hlth.Org. techn.Rep.Ser., 131.015p049
15 Referred to as "classified information on narcotics" in the ninth report of the Expert Committee on Addiction-producing Drugs, Wld.Hlth.Org. techn.Rep.Ser., 1959, 160, 14.016p049
16 Unpublished working document WHO/Av. Med./1.017p049
17 United Nations Commission on Narcotic Drugs. The Single Convention on Narcotic Drugs (Third Draft) (mimeographed document E/CN.7/AC.3/9).018p049
18 Wld.Hlth.Org. techn.Rep.Ser., 1959, 160, 12 (section 10.1).019p049
19 Wld.Hlth.Org. techn.Rep.Ser., 1956, 102, 4 (section 3.1).020p049
20 Wld.Hlth.Org. techn.Rep.Ser., 1957, 116, 5 (section 4.1).021p049
21 Wld.Hlth.Org. techn.Rep.Ser., 1958, 142, 5 (section 4.1).022p049
22 United Nations Commission on Narcotic Drugs. Report on the tenth session (18 April-12 May 1955) - (Economic and Social Council Official Records: twentieth session. Supplement No. 8), Geneva, p. 42 (Document E/2768/Rev.1 - E/CN.7/303/Rev.1).