WORLD HEALTH ORGANIZATION EXPERT COMMITTEE ON DRUG DEPENDENCE

The World Health Organization (WHO) originated from a proposal at the first United Nations (U.N.) conference held in San Francisco in 1945 that "a specialized agency be created to deal with all matters related to health." This proposal resulted in a draft WHO constitution signed by sixty-one governments at an international health conference held in New York City in 1946. The constitution was subsequently ratified by the twenty-six member states of the U.N. and came into force on April 7, 1948. The enormous proposed scope of WHO led to the early concept of "Expert Committees," and they have become an essential part of the machinery of the organization. Their function is to give technical advice to WHO. Members of these committees are "appointed by the Director-General, in accordance with regulations established by the Executive Board." The members are chosen for their "abilities and technical experience" with "due regard being paid to adequate geographical distribution." Reports of expert committees can only be published with the authorization of the World Health Assembly or the WHO executive board.

One of the first tasks of the U.N. and WHO was to pick up the regulatory work on addiction-producing drugs that had been initiated and carried out by the League of Nations. Thus, the Expert Committee on Habit-Forming Drugs was established in 1948 to provide expert technical advice to the U.N. Permanent Central Opium Board and Drug Supervisory Body and the Division of Narcotic Drugs. The first meeting of the expert committee was held January 24-29, 1949, at the Palais des Nations in Geneva, Switzerland, where it continued to meet until the WHO building was opened in 1961. The expert committee, in its report on the second session, felt that the expression "habit forming" was no longer appropriate and recommended that the designation of the committee be changed to Expert Committee on Drugs Liable to Produce Addiction. This change was adopted by the WHO executive board at its fifth session and remained until 1964, when it was altered to Expert Committee on Dependence Producing Drugs and finally in 1968 to its present designation, Expert Committee on Drug Dependence.

In its early years, the expert committee reported directly to the director-general of WHO through its own secretary. In 1965, it became part of the Division of Pharmacology and Toxicology. During much of the period from its inception to 1972, the Seretariat was in the hands of Dr. Hans Halbach. In 1977, the expert committee became part of the Division of Mental Health, under the direction of Dr. Inayat Khan, where it remained until 1990 when a new Programme on Substance Abuse was created.

The early meetings of the expert committee were mainly devoted to the opioids—including the natural products, semisynthetics, and synthetics. Notifications on specific compounds by individual nations were responded to and recommendations as to international control were communicated to the secretary-general of the U.N. The beginnings of often recurring discussions were initiated concerning definitions, methods for evaluating dependence liability in animals and humans, the need for accurate epidemiological data concerning the extent of abuse and public health problems associated with drugs in general and of specific compounds in particular. During this period, the expert committee had an important consultative role in the development of a new international drug-control treaty, which resulted in an international conference held in New York City in January 1961. From this Conference emerged the Single Convention on Narcotic Drugs, 1961. This convention was amended in 1972, again with strong input from the expert committee, and remains the current instrument for the international control of the opioids, cocaine, and cannabis (marijuana).

The committee's concern for the potential abuse of the newly emerging ataractics (tranquilizing drugs) began in the mid-1950s and was soon joined in the 1960s by discussions of the problems created by amphetamines, amphetamine-like drugs, and hallucinogens. The difficulties associated with controlling these new heterogeneous groups of drugs under the Single Convention of 1961 became apparent and, at its seventeenth meeting in 1969, the committee began discussions of a draft Protocol on Psychotropic Substances, developed by the U.N. Commission on Narcotic Drugs, which formalized a classification of psychotropic drugs developed by the expert committee at its sixteenth meeting in 1968. The increasingly serious international public-health problems created by these drugs led the United Nations to hold a conference for the Adoption of a Protocol on Psychotropic Substances held in Vienna in February 1971; this resulted in the Convention on Psychotropic Substances, 1971, which the United Nations finally ratified in 1976. One important feature of this convention is that it mandates a WHO assessment of a substance prior to control and states that WHO's "assessments shall be determinative as to medical and scientific matters." This mandate added great responsibility to the functional role of the expert committee.

Only two meetings of the expert committee were held between the adoption of the Convention on Psychotropic Substances in 1971 and its ratification in 1976. The nineteenth meeting in 1972 was mainly devoted to a review of the current status of the epidemiological study of drug dependence. This meeting was also the last attended by Dr. Nathan B. Eddy, before his death in 1973. Dr. Eddy, a giant in the study of drug abuse and dependency, was at all the first nineteen meetings and served as chairman or rapporteur for most of them. The twentieth meeting of the committee was essentially devoted to the topic of prevention and resulted in a thorough review of the literature and a series of conclusions and recommendations, which were of considerable influence in the future development of the field.

The twenty-first meeting of the committee was held in 1977. It was entirely concerned with consideration of the Convention on Psychotropic Substances, and how WHO would handle its obligations under the treaty. This included consideration of appropriate pharmacological studies in animals and humans, assessment of public-health and social problems, assessment of therapeutic usefulness, the problem of chemically generic extensions to the list of scheduled substances, and the decision-making process. The meeting resulted in a number of recommendations that were mainly concerned with international cooperation in the development and collection of the relevant data needed to make rational decisions on controlling substances under the convention.

The expert committee did not meet formally again until 1985. In the interim, however, a number of WHO ad-hoc committees met to consider various aspects of the implementation of the treaty. In 1980, an extensive review of the Assessment of Public Health and Social Problems Associated with the Use of Psychotropic Drugs was carried out. To assist WHO, the U.S. National Institute on Drug Abuse, in collaboration with the Committee on Problems of Drug Dependence, published a monograph on "Testing Drugs for Physical Dependence Potential and Abuse Liability," which updated a similar WHO report published a decade earlier. A particularly difficult section of the psychotropic convention concerns exempt preparations. This involves thousands of pharmaceutical products and how to handle them, and it has still not been completely resolved despite three meetings of WHO advisory groups in 1977, 1982, and 1984.

Initially, to handle WHO's necessary functions under the conventions, it was decided to use ad-hoc advisory groups rather than to call formal meetings of the expert committee. The first of these was held in 1978. In 1979, specific compounds were considered under both conventions and the recommendation was made that, in the future, compounds proposed for control under the psychotropic convention be considered by class. In 1980, nine anorectic substances (things that cause loss of appetite) were reviewed and recommendations as to control were forwarded. Discussions concerning Khat and its active principals, cathine and cathinone, were begun and research was initiated by a widespread group of laboratories. In 1981, the mixed opioid Agonist-Antagonist drugs were reviewed, and in 1981 and 1982 the Benzodiazepines as a class were reviewed and recommendations for control were sent to the U.N. Also during this period a more formal method for review emerged from discussions with the U.N. Commission on Narcotic Drugs and the WHO Executive Board. Detailed critical reviews of substances to be considered for control were developed and the Programme Planning Working Group was formed to review these and suggest future classes of compounds for review by the expert committee. Two additional ad hoc advisory committee meetings were held in 1983 and 1984 to consider a variety of individual compounds and exempt preparations.

The twenty-second meeting of the expert committee was held in Geneva in April 1985. The committee adopted the new procedures for review of substances recently approved by the WHO Executive Board. These guidelines mandated a procedural sequence and schedule for the review. WHO was to obtain detailed information on each substance from a wide variety of sources including individual experts, research groups (e.g., WHO Collaborating Centers), the pharmaceutical industry, and relevant publications. It should be noted that this was the first time that the pharmaceutical industry was included in deliberations concerning regulatory control of their products. The twenty-second meeting was held, primarily, to consider twenty-eight phenethylamines for control under the Psychotropic Convention. A large number of groups and individuals was involved in preparing the critical review of these substances. Many of the substances considered were recommended for control under various schedules of the Psychotropic Convention. Some were not considered to need control, and no recommendation was made on these. Among the recommendations emerging from this meeting were requests for more and better data, particularly epidemiological, and more consideration of structure-activity relationships, isomeric state, and drug metabolism.

The twenty-third meeting in 1986 was nearly entirely devoted to the review of thirty-one Barbiturates. A number of new factors were considered in the deliberations on this group of drugs. These included therapeutic indication (e.g., ultrashort-acting intravenous anesthetics, intermediate-acting sedative-hypnotics, and anticonvulsants), therapeutic usefulness, and demonstrable international public-health and social problems. Particular concern was expressed concerning Phenobarbital, an inexpensive, effective antiepileptic widely used in developing countries, since it was felt by some that international control might lead to the use of more expensive and less safe medications. The committee also noted a lack of data on many compounds concerning dependence potential from either animals or controlled clinical studies and recommended that this be systematically collected by WHO prior to consideration for control.

The twenty-fourth meeting in 1987 discussed the control of seven nonbarbiturate sedative hypnotics. None of these were recommended for control. The committee also considered the marked increase in the illicit traffic in Secobarbital and recommended that it be moved from Schedule III to Schedule II of the Psychotropic Convention. Finally, the committee recommended control of a number of fentanyl and Meperidine analogs under the Single Convention.

The twenty-fifth meeting in 1988 considered the control of an additional four nonbarbiturate sedative-hypnotics including Methaqualone, which had been suggested for control in Schedule I of the Psychotropic Convention at the twenty-fourth expert committee meeting. Of these compounds, only methaqualone was recommended for control. The committee did not recommend rescheduling to Schecule I but urged the secretary-general of WHO that "every effort should be made to urge all countries whether or not they are signatories to the Convention on Psychotropic Substances, 1971, to stop producing methaqualone and to ban its import or export." The expert committee also revisited the opioid agonist-antagonist analgesics and recommended that Buprenorphine and pentazocine be controlled under Schedule III of the Psychotropic Convention. This was a significant departure and was the first time that compounds with some opioid-like properties were considered for control under this convention rather than the Single Convention, 1961. A number of other compounds were considered for control, the most interesting being propylhexadrene. This substance was the first to be considered for decontrol under the Psychotropic Convention. The committee recommended that additional epidemiological data be collected and the substance reviewed again in two years. This was done in 1990, and a recommendation to remove propylhexadrene from control was forwarded to the U.N. secretary-general.

The twenty-sixth meeting of the committee in 1989 considered four additional uncontrolled benzodiazepines and recommended control for only one. The remainder were held over for the twenty-seventh meeting, in which the 33 benzodiazepines already under control were to be reviewed. This meeting also recommended the control of a number of "Designer Drugs," including analogs of fentanyl, tenamfetamine (MDA), and aminorex. Also considered was the notification from the government of the United States to transfer delta -9-tetrahydrocannabinol, the active principle of Marijuana, from Schedule I to Schedule II of the Convention on Psychotropic Substances. The committee so recommended, with the exception of two members who felt the decision should be deferred for additional data concerning therapeutic usefulness.

The twenty-seventh and last meeting to date of the expert committee was held in 1990 and was essentially devoted to the scheduling of the benzodiazepines as a class. Of particular interest was the conclusion that differential scheduling of the benzodiazepines was possible. Thus, the committee recommended that of the thirty-three substances currently under control, nineteen were appropriately controlled under Schedule IV. Thirteen of the substances had moderate to high therapeutic usefulness and few or no reports of abuse or illicit activity, and the committee declared that WHO should "monitor these compounds to amass enough data to determine whether or not they should be placed under critical review to consider descheduling." Two compounds, diazepam and flunitrazepam, "showed a continuing higher incidence of abuse and association with illicit activity." It was recommended that WHO keep these compounds under surveillance "to determine whether or not they merit being placed under critical review to consider appropriate scheduling."

As a result of structural changes within WHO and the creation of the new Programme on Substance Abuse, it is clear that in the future the expert committee will change its focus from reviewing substances for control under the international conventions to a broader consideration of the issues of prevention and reduction of demand.

(See also: Abuse Liability of Drugs: Testing in Humans )

BIBLIOGRAPHY

Encyclopaedia Britannica, vol 13, 232-233.

Handbook of Resolutions and Decisions of the World Health Organization Assembly and the Executive Board, vols. I and II. Geneva: World Health Organization, 1985.

W.H.O. What it is, WHAT IT DOES. Geneva: World Health Organization, 1988.

Louis Harris

UNITED NATIONS CONVENTION AGAINST ILLICIT TRAFFIC IN NARCOTIC DRUGS AND PSYCHOTROPIC SUBSTANCES, 1988

This international treaty was intended to extend and augment the agreements among the signatories that were contained in the 1961 Single Convention on Narcotic Drugs and the 1971 Convention on Psychotropic Substances. The 1988 Convention came into force in November 1990. By November 1994, 103 governments and the European Economic Community had been parties to the Convention. Included among the provisions are arrangements and agreements to legalize seizure of drug-related assets; criminalize Money Laundering; relax bank-secrecy rules; permit extradition of individuals charged with drug-law violations; control shipments of precursor and essential chemicals; continue to support Crop Control and eradication; and share evidence with law enforcement and prosecuting agencies of governments who are party to the conventions.

BIBLIOGRAPHY

U.S. Department of Justice, Office of Justice Programs, Bureau of Justice Statistics. (1992). Drugs, crime and the justice system (December NCJ-133652). Washington, DC: U.S. Government Printing Office.

Jerome H. Jaffe