European Journal of Palliative Care, 1997: 4(6) 194-198.
Carmen Selva outlines the work of the International Narcotics Control Board (INCB)
For many centuries plants and their extracts have been used for the treatment of diseases. Opium and its derivatives, also known as opiates, were considered to be natural drugs useful in medicine for their analgesic properties. Opium is the exuded latex obtained by incision into the unripe capsules of the poppy plant. This is the raw opium, and it may contain up to 25 different alkaloids, with morphine and codeine being the more important.
In some of the countries where raw opium is produced, this material is processed into medicinal opium preparations or is collected and dried for the further extraction of morphine. The industrial extraction of alkaloids from the poppy plant, once ripe and dry, is carried out through a chemical process in several countries.
Opioid is the usual term used to designate drugs derived from opium and their chemically related derivatives such as the semisynthetic drugs with morphine-like actions, although the chemical structure may differ from that of morphine. However, from a clinical point of view, opioids are more accurately classified according to their actions compared with those of morphine - similar affinity (agonist), competitive (antagonist) or mixed (agonist/antagonist) - on the same receptor sites (so-called opioid receptors) in the central and peripheral nervous system.1
Key Points:
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By definition, 'narcotics' are substances inducing sleep and drowsiness, but in the context of international control the expression 'narcotic drug' is a legal term and means any substance, whether natural or synthetic, listed in Schedules I and II of the 1961 Single Convention on Narcotic Drugs.
The use of opium and its derivatives is well known to alleviate pain, cough and diarrhoea, particularly in countries where poppy plants are cultivated and widely used by popular tradition. Unfortunately, its misuse constitutes a risk to public health, and therefore its medical use and export to other countries led to international agreements being established for its control.
Opium was the drug that motivated the first conference dealing with matters of drug control. This meeting, known as the Opium Commission Forum, was held in Shanghai in 1909 and attended by representatives from 13 countries. Growing addiction problems in Far Eastern countries and the development of the opium trade led to the first Drug Control Treaty, signed at The Hague in 1912. The parties to this treaty agreed to limit the manufacture, trade and use of opium for strictly medical purposes.
After the Second World War, with the expansion of the pharmaceutical industry, new products were synthesised that also produced dependency effects. These drugs were included in the scope of international control by subsequent conventions and protocols. The International Opium Convention of 1925 established for the first time a statistical system of control over the production, manufacture, trade and distribution of narcotic drugs and a permanent Central Board to supervise the system. In the Convention of 1931, governments were for the first time required to supply annual estimates of their needs for manufactured narcotic drugs with a view to limiting the supplies of such drugs to the quantities needed solely for medical and scientific purposes.
To take account of the prevailing situation, additional legal instruments were progressively developed and later amalgamated into a unified treaty - the 1961 Single Convention2 - which marked a major milestone in the history of international narcotics control. The Convention simplified the international control machinery by creating the International Narcotics Control Board (INCB) to replace the previous bodies. It also introduced a regulatory system for the cultivation of the raw materials of natural narcotic drugs. The Single Convention was further strengthened by the 1972 Protocol, which highlighted the need to provide treatment and rehabilitation services to drug addicts and promote social reintegration, as well as the need for co-operative and co-ordinated international action.
The success of the Single Convention is particularly evident with regard to the limitation of the cultivation, production, manufacture, trade, distribution and use of narcotic drugs for medical and scientific purposes, and the prevention of diversion from licit sources into illicit channels.3 Diversion from licit sources into illicit trade has been kept to a minimum despite the large volume of trade.
At present, control is exercised under the Single Convention over 116 narcotic drugs including their pharmaceutical preparations. These include mainly natural products such as opium and its derivatives - morphine, codeine and diamorphine - but also synthetic narcotic drugs such as methadone and pethidine, as well as cannabis and cocaine. The measures of control that the Convention prescribes vary in severity from one group of drugs to another. For this purpose, drugs are listed in four Schedules annexed to the Convention according to the differences in their dependence producing properties, therapeutic value and risk of abuse.
Various specialised agencies of the United Nations are involved in certain aspects relating to drug control, but only the World Health Organisation (WHO) is specifically given a role by the international drug control treaties concerning the scope of substances under restriction. Upon the medical and scientific consideration of WHO, a drug can be added to one of the Schedules of the Convention.
The INCB is a panel of 13 member experts serving in their personal capacity. Its responsibility is to promote governments' compliance with the treaties in the interest of the international community as a whole. The INCB maintains a permanent dialogue with governments, performs country missions when it is deemed necessary and organises training seminars for drug control administration officers.
The statistical data supplied to the Board by national governments is the main source of the INCB's information. The quality of the statistical information on licit drugs depends on the control exercised at national level. This data should cover the estimated requirements of narcotic drugs for a year by a particular country, including imports and exports, as well as their production, manufacture, use, consumption, stocks and seizures.
These statistics give an exact picture of the movement of narcotic drugs in each country, enabling the Board to perform the functions of surveillance conferred upon it by the Single Convention. The Board verifies that the supply and availability of opioids are sufficient during the corresponding year. The Board also monitors governments' compliance with the provisions of the other two international drug control treaties, namely the 1971 Convention on Psychotropic Substances and the 1988 Convention against Illicit Traffic in Narcotic Drugs and Psychotropic Substances.
As part of its mandate, the Board publishes an annual report that provides a comprehensive survey of the world drug situation. As an impartial observer, the INCB tries to identify and predict dangerous trends and suggest measures to counteract them. It produces two technical publications on narcotic drugs and psychotropic substances and other reports.
Opioids are mainly used for analgesia - acute or severe pain (eg, morphine, pethidine), mild to moderate pain (eg, codeine, dextro propoxyphene) - induction or supplementary anaesthesia (fentanyl), as cough suppressants (codeine and, to a lesser extent, pholcodine and ethylmorphine), in gastrointestinal disorders, mainly diarrhoea (codeine, diphenoxylate), and for the treatment of addiction to opioids. Some opioids, like hydrocodone or oxycodone, are compounded in mixtures with non-opioid drugs (as analgesic-antipyretic combinations) to provide analgesic action while preventing adverse narcotic effects.
The availability of different analgesics in each country allows for a wide range of alternatives in the selection of agents for specific situations. This partly explains the vast differences between countries, reflected in the quantities used of a particular drug. Differences may be due to several factors, such as the specific control regulations in a particular country, the development and manufacture of the respective opioid drug by a pharmaceutical industry established in that country or the physicians' prescribing practices with respect to opioid analgesics. To illustrate this point, consumption trends for the main licit drugs are summarised in Table 1.4
Table 1. World consumption in kg of the main narcotic drugs in 1995 |
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| Opium alkaloids and derivatives | Synthetic narcotic drugs | |||
| Codeine | 181,421 | Dextropropoxyphene | 252,483 | |
| Dihydrocodein | 27,340 | Pethidine | 15,104 | |
| Morphine | 15,594 | Tildine | 8,529 | |
| Pholcodine | 9,089 | Diphenoxylate | 6,490 | |
| Hydrocodone | 8,869 | Methadone | 6,337 | |
| Ethylmorphine | 2,689 | Fentanyl | 94 | |
| Source: Narcotic drugs: Estimated world requirements for 1997. Statistics for 1995. New York: United Nations, 1997.4 | ||||
The dominant feature in the use of morphine since the second half of the 1980s has been the continuous increase in the quantities used for the treatment of pain. Available information shows that the total amount of morphine consumed for medication in 1995 stood at 15.6 tonnes (Figure 1).
Figure 1. Global consumption of morphine for medication, 1976-1995
Although codeine is a natural alkaloid obtained from opium and poppy straw, most codeine is manufactured by semisynthesis. Codeine represents the bulk of the licit opiate consumption. It is used mainly as an analgesic or cough suppressant. During the past two decades, global codeine consumption has fluctuated at around 160 tonnes per year. In 1993, consumption rose to over 175 tonnes and, in 1995, it reached the highest level, totalling 181.4 tonnes (Figure 2).
Figure 2. Global consumption of codeine for medication, 1976-1995
Methadone is a synthetic opioid chemically different from, but with broadly similar pharmacological qualities to, morphine. Due to its effective analgesic activity and long duration of action after oral administration, methadone is particularly useful in chronic painful conditions because it can prevent or relieve acute withdrawal symptoms produced by morphine-like drugs. It is also used in the detoxification treatment of patients dependent upon these agents as well as in maintenance programmes for individuals dependent on diamorphine or other opioids. For these reasons, worldwide methadone consumption, which rose steadily from 1.6 tonnes in 1980 to 5.3 tonnes in 1994, reached a new record of 6.3 tonnes in 1995.
This was one of the first opioids to be used as a parent drug in clandestine laboratories to synthesise more potent derivatives, such as the so-called 'designer' drugs. It is almost one hundred times more potent than morphine.
Fentanyl is used, in very small doses (eg, 0.005-0.1 mg in injectable form), as an analgesic or for the induction of anaesthesia and in combination with other substances for a balanced anaesthesia in short-term surgical interventions. It has recently become available as a transdermal preparation (patches) for chronic pain. With similar actions, other fentanyl derivatives, namely alfentanil and sufentanil, are increasingly being used in medicine (sufentanil is around ten times as potent as fentanyl).
However, while certain fentanyl analogues are particularly potent drugs (over one thousand times more potent than morphine), they are not used in medicine because of their adverse effects. The world consumption of fentanyl in 1995 was 94 kg.
Among the reasons for the increasing trend in worldwide licit consumption of opioids are the following:
Trends indicate that the medical use of narcotic drugs is likely to increase6 (Table 1). However, figures known to the Board also indicate that several countries are far from achieving the rational use of essential drugs to alleviate pain. For instance, for countries with a population of more than ten million, such as Morocco, Peru and Venezuela, statistical data shows that less than 1 kg of morphine had actually been consumed in 1995, representing a much lower amount than the estimated amount required. Some of these countries have already started adjusting their estimate of their needs as significant changes in their future projections have been reported to the Board.
The operation of the international drug control system is based on the principles of national legislation and enforcement by states and their co-operation between other states and United Nations' bodies. The INCB notes that morphine consumption has increased rapidly due to the initiatives of WHO in the treatment of pain and suffering. Consumption of morphine is likely to continue increasing, especially in countries that are beginning or expanding their outpatient cancer relief programmes.
Governments should establish national drug control measures in compliance with the United Nations' binding international treaties and, at the same time, adopt policies to ensure the availability of essential drugs for pain relief programmes.7
A study conducted by the INCB6 in 1995 on the availability of opioids for pain management worldwide shows that in many countries opioids are still unavailable for medical needs. From the 65 governments (mainly from developed countries and representing 50% of the world's population) that responded to the INCB survey, only 36 reported having investigated the reasons for this.
Impediments to opioid availability include concerns about drug addiction, diversion and restrictive legislation on drug control. While only 48% of governments reported that morphine in any form was available in all their cancer treatment hospitals, 54% of governments reported having periodic shortages in opioids, mainly due to insufficient importation, distribution delays and administrative problems in their national health systems.
WHO guidelines recommend that opioids should be available for cancer patients at hospital and community levels and that physicians should be able to prescribe narcotic drugs according to the individual needs of each patient. While most governments allow physicians to prescribe opioids for patients, requirements vary among nations. This may include filling in special government prescription forms, obtaining permission of the hospital or the medical supervisor, special license or training and a maximum quantity of morphine that may be prescribed at any one time or a maximum length of administration for a patient who lives at home. Other obstacles to opioid administration are concerns about addiction (even though WHO considers that cancer patients who are physically dependent do not fulfil the criteria for drug dependency)5 and reluctance from health professionals to prescribe opioids out of concern for the possibility of legal sanctions. However, diversion to illicit channels is not the main area of concern, as it is well known that this is kept under control.
Considering the efficacy that the international narcotics control system is demonstrating in preventing the diversion of drugs, while at the same time facilitating the development of pain relief programmes, it is important that all agents involved co-operate with the licit control effort. In special cases, healthcare professionals are encouraged to communicate with government regulators and work together to make the necessary arrangements for ensuring that opioids are available for medical purposes, as is intended under international law.8
Pain management experts and medical associations should be aware of the national estimate of the amount of opioids that is needed. Current information about pain management and the need to train healthcare personnel will be valuable to regulators whose job it is to look after the integrity of the distribution system. Since a consistent availability of pain medications to patients is essential, the INCB is calling for the attention of governments to look into this matter and recommends that they revise their methods of estimating medical needs for opioids.
More than half of the governments that responded to the 1995 INCB survey6 said that they had not examined their methods, although 60% had asked for supplementary estimates in the last five years due to unforeseen increases in the demand for opioids by the medical profession.
The Board will continue its examination of the global situation by increasing its monitoring of annual estimates furnished by governments to ensure that they are neither over- nor underestimated.
1. AG Gilman (ed). The Pharmacological Basis or Therapeutics (international
edition). Maidenhead: McGraw Hill, 1992: 485-521.
Carmen Selva, Head of the Narcotics Drugs
Estimates Unit, International Narcotics Control
Board Secretariat, United Nations Vienna
International Centre, Austria
