Current Scheduling Status
Year(s) and type of review / ECDD meetings
Drug Class
Recommendation (from TRS)
Substance identification
Methaqualone (INN, CAS 72-44-6) is 2-methyl-3-o0-tolyl-4(3 H)-quinazolinone. No stereoisomeric forms are possible.
WHO review history
Methaqualone was included in Schedule IV of the original draft of the Convention on Psychotropic Substances, 1971, and came under international control when the Convention was enforced. However, because of diversion of methaqualone into illicit channels and increased evidence of its abuse, it was placed in-1979 in Schedule I of the Convention following a recommendation by WHO (8). In 1987, at its twenty-fourth meeting, the Expert Committee on Drug Dependence reviewed non-barbiturate sedatives and hypnotics and considered the need to recommend rescheduling methaqualone to Schedule I of the 1971 Convention (2). It became clear that many countries had withdrawn methaqualone from the market because of widespread abuse and serious illicit trafficking. The Committee recommended a thorough re-examination of the situation and the inclusion of methaqualone in the critical review document for formal consideration at its twenty-fifth meeting. The Committee agreed that methaqualone should be considered in accordance with established WHO procedures for the review of psychoactive substances and was of the opinion that the Secretary-General of the United Nations should notify the governments of Member countries that the drug was being considered for rescheduling to Schedule I. During 1987, when data were being collected for the critical review document for consideration by the Expert Committee, explicit information on methaqualone was requested in communications from the Secretary-General of the United Nations and from the Director General of WHO to Member countries. In addition, the records of the International Narcotics Control Board and of INTERPOL on the use and abuse of methaqualone were available to WHO.
Similarity to known substances and effects on the CNS
Methaqualone is a depressant of the central nervous system similar in its actions and effects to the barbiturates. In addition to sedative-hypnotic properties, methaqualone possesses anticonvulsant, antispasmodic, local anaesthetic and weak antihistaminic properties. It also has antitussive activity comparable with that of codeine. Cases of acute intoxication, methaqualone-related suicides, and deaths in drug abusers due to methaqualone overdoses have been reported in several countries.
Dependence potential
Methaqualone is known to produce tolerance and physical dependence of the barbiturate type in animals and humans. It is self administered by rhesus monkeys and produces euphoria as well as pentobarbital-like subjective effects in humans.
Actual abuse and or/evidence of likelihood of abuse
Methaqualone has been widely abused, mainly by young people, particularly in such countries as. the Federal Republic of Germany, Japan and the USA. It has been reported to produce a dissociative "high", without the drowsiness caused by barbiturates. Some abusers state that the effects resemble those of opiate drugs. Methaqualone is often taken with diphenhydramine by drug abusers; methaqualone preparations containing diphenhydramine (e.g., Mandrax) have been frequently abused in south-east Asia, and a preparation of this type has been. reported to be very popular among heroin-dependent users in the United Kingdom. Part of the attraction of the substance as a drug of abuse may be linked to a belief among users that the drug reduces sexual inhibitions. Because of substantial abuse problems, methaqualone has been removed from the market by government action in many countries,
and production has been reduced or stopped by a number of pharmaceutical manufacturers. Severe depression of the central nervous system may occur when methaqualone is taken in combination with ethanol or other depressants of the central nervous system. The symptoms of acute poisoning are quite similar to those produced by the barbiturates and most other hypnotics. Severe overdose of methaqualone in combination with diphenhydramine results in tachycardia, restlessness, delirium, hypertonia and hyper-reflexia, convulsion, coma and sometimes death. Data available to the International Narcotics Control Board show that annual legal consumption of methaqualone amounts to approximately 20 tonnes and is distributed among 33 countries and regions. In the large majority of states and regions, namely 153 of the 186 defined in the Convention on Psychotropic Substances, 1971, methaqualone is not used for medical purposes. Three countries account for 60%, i.e., approximately 12 tonnes, of the total consumed. Data from 22 countries, including ten developing countries in Africa but not including the United States, show that more than 7 million tablets were seized in 1987. It is not clear how much of this methaqualone was diverted from legitimate production and how much was produced in clandestine laboratories. Over the past few years a number of illicit laboratories have been discovered and closed. Recently, successful efforts to prevent the establishment of at least- one large-scale clandestine laboratory in Africa probably helped to keep the illicit supply from increasing still further.
Therapeutic usefulness
Methaqualone has been used as a hypnotic and sedative, its hypnotic effect being reported to be enhanced by diphenhydramine. The therapeutic usefulness of methaqualone has been reviewed by WHO several times in the past (e.g., 8), and it was concluded that it has no particular advantages over other available hypnotics. Because of the high abuse liability of methaqualone and the serious social problems caused by such abuse, the drug has been replaced by others in medical practice in many countries. Its use as a therapeutic agent is becoming progressively more limited as more countries remove it from the market.
Recommendation
On the basis of the available data concerning its pharmacological profile, dependence potential, and particularly its actual abuse over the past decade, the Committee rated the dependence potential and abuse liability of methaqualone’ as. high, in agreement with a previous WHO review group (8). The drug continues to. be shipped illegally across international boundaries. Information made available: to the Expert Committee showed that, even when specifically advised that the drug was being considered for rescheduling from Schedule II to Schedule I of the Convention on Psychotropic Substances, 1971, no-country indicated that methaqualone had any special therapeutic advantages that would strongly argue for its continued availability in the face of the public health and social problems associated with its abuse. Such problems persist because methaqualone remains available and illicit
traffic in it continues despite its rescheduling to Schedule IT of the Convention in 1979. Although methaqualone 1 is still available for legitimate clinical use in 33 countries and regions, the Committee judged that the extent of the abuse and of the public health and social problems associated with this substance on-an international: scale might warrant its placing under even stricter controls under the terms of the Convention on Psychotropic Substances, 1971, i.e. rescheduling it to Schedule I if such a shift was consistent with the terms of the Convention. In making this judgement, the Committee weighed the therapeutic usefulness of the drug, the extent and persistence of public health and social problems associated with its use, and the
availability of other satisfactory therapeutic alternatives. The Committee was aware that the placing of a drug having some medical usefulness, however modest, in Schedule I, together with agents that have no medical usefulness whatsoever, might be establishing a precedent not intended by the Convention. The Committee was also aware -that :not all-countries where
methaqualone is produced are signatories to the Convention, that it is relatively easy to synthesize and that clandestine production might well replace the diversion from legitimate production, if any, that now supplies the illicit traffic. The Committee. was unanimous in recommending to the Director 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. Furthermore, countries now using methaqualone for medical purposes should be strongly encouraged to end such use’so as to reduce the need for its legitimate production anywhere in the world. The Committee further recommended that the Director General of WHO should continue to collect data on the use of the drug and to submit it for consideration by the WHO Expert Committee at some future date.
Methaqualone (INN, CAS 72-44-6) is 2-methyl-3-o0-tolyl-4(3 H)-quinazolinone. No stereoisomeric forms are possible.
WHO review history
Methaqualone was included in Schedule IV of the original draft of the Convention on Psychotropic Substances, 1971, and came under international control when the Convention was enforced. However, because of diversion of methaqualone into illicit channels and increased evidence of its abuse, it was placed in-1979 in Schedule I of the Convention following a recommendation by WHO (8). In 1987, at its twenty-fourth meeting, the Expert Committee on Drug Dependence reviewed non-barbiturate sedatives and hypnotics and considered the need to recommend rescheduling methaqualone to Schedule I of the 1971 Convention (2). It became clear that many countries had withdrawn methaqualone from the market because of widespread abuse and serious illicit trafficking. The Committee recommended a thorough re-examination of the situation and the inclusion of methaqualone in the critical review document for formal consideration at its twenty-fifth meeting. The Committee agreed that methaqualone should be considered in accordance with established WHO procedures for the review of psychoactive substances and was of the opinion that the Secretary-General of the United Nations should notify the governments of Member countries that the drug was being considered for rescheduling to Schedule I. During 1987, when data were being collected for the critical review document for consideration by the Expert Committee, explicit information on methaqualone was requested in communications from the Secretary-General of the United Nations and from the Director General of WHO to Member countries. In addition, the records of the International Narcotics Control Board and of INTERPOL on the use and abuse of methaqualone were available to WHO.
Similarity to known substances and effects on the CNS
Methaqualone is a depressant of the central nervous system similar in its actions and effects to the barbiturates. In addition to sedative-hypnotic properties, methaqualone possesses anticonvulsant, antispasmodic, local anaesthetic and weak antihistaminic properties. It also has antitussive activity comparable with that of codeine. Cases of acute intoxication, methaqualone-related suicides, and deaths in drug abusers due to methaqualone overdoses have been reported in several countries.
Dependence potential
Methaqualone is known to produce tolerance and physical dependence of the barbiturate type in animals and humans. It is self administered by rhesus monkeys and produces euphoria as well as pentobarbital-like subjective effects in humans.
Actual abuse and or/evidence of likelihood of abuse
Methaqualone has been widely abused, mainly by young people, particularly in such countries as. the Federal Republic of Germany, Japan and the USA. It has been reported to produce a dissociative "high", without the drowsiness caused by barbiturates. Some abusers state that the effects resemble those of opiate drugs. Methaqualone is often taken with diphenhydramine by drug abusers; methaqualone preparations containing diphenhydramine (e.g., Mandrax) have been frequently abused in south-east Asia, and a preparation of this type has been. reported to be very popular among heroin-dependent users in the United Kingdom. Part of the attraction of the substance as a drug of abuse may be linked to a belief among users that the drug reduces sexual inhibitions. Because of substantial abuse problems, methaqualone has been removed from the market by government action in many countries,
and production has been reduced or stopped by a number of pharmaceutical manufacturers. Severe depression of the central nervous system may occur when methaqualone is taken in combination with ethanol or other depressants of the central nervous system. The symptoms of acute poisoning are quite similar to those produced by the barbiturates and most other hypnotics. Severe overdose of methaqualone in combination with diphenhydramine results in tachycardia, restlessness, delirium, hypertonia and hyper-reflexia, convulsion, coma and sometimes death. Data available to the International Narcotics Control Board show that annual legal consumption of methaqualone amounts to approximately 20 tonnes and is distributed among 33 countries and regions. In the large majority of states and regions, namely 153 of the 186 defined in the Convention on Psychotropic Substances, 1971, methaqualone is not used for medical purposes. Three countries account for 60%, i.e., approximately 12 tonnes, of the total consumed. Data from 22 countries, including ten developing countries in Africa but not including the United States, show that more than 7 million tablets were seized in 1987. It is not clear how much of this methaqualone was diverted from legitimate production and how much was produced in clandestine laboratories. Over the past few years a number of illicit laboratories have been discovered and closed. Recently, successful efforts to prevent the establishment of at least- one large-scale clandestine laboratory in Africa probably helped to keep the illicit supply from increasing still further.
Therapeutic usefulness
Methaqualone has been used as a hypnotic and sedative, its hypnotic effect being reported to be enhanced by diphenhydramine. The therapeutic usefulness of methaqualone has been reviewed by WHO several times in the past (e.g., 8), and it was concluded that it has no particular advantages over other available hypnotics. Because of the high abuse liability of methaqualone and the serious social problems caused by such abuse, the drug has been replaced by others in medical practice in many countries. Its use as a therapeutic agent is becoming progressively more limited as more countries remove it from the market.
Recommendation
On the basis of the available data concerning its pharmacological profile, dependence potential, and particularly its actual abuse over the past decade, the Committee rated the dependence potential and abuse liability of methaqualone’ as. high, in agreement with a previous WHO review group (8). The drug continues to. be shipped illegally across international boundaries. Information made available: to the Expert Committee showed that, even when specifically advised that the drug was being considered for rescheduling from Schedule II to Schedule I of the Convention on Psychotropic Substances, 1971, no-country indicated that methaqualone had any special therapeutic advantages that would strongly argue for its continued availability in the face of the public health and social problems associated with its abuse. Such problems persist because methaqualone remains available and illicit
traffic in it continues despite its rescheduling to Schedule IT of the Convention in 1979. Although methaqualone 1 is still available for legitimate clinical use in 33 countries and regions, the Committee judged that the extent of the abuse and of the public health and social problems associated with this substance on-an international: scale might warrant its placing under even stricter controls under the terms of the Convention on Psychotropic Substances, 1971, i.e. rescheduling it to Schedule I if such a shift was consistent with the terms of the Convention. In making this judgement, the Committee weighed the therapeutic usefulness of the drug, the extent and persistence of public health and social problems associated with its use, and the
availability of other satisfactory therapeutic alternatives. The Committee was aware that the placing of a drug having some medical usefulness, however modest, in Schedule I, together with agents that have no medical usefulness whatsoever, might be establishing a precedent not intended by the Convention. The Committee was also aware -that :not all-countries where
methaqualone is produced are signatories to the Convention, that it is relatively easy to synthesize and that clandestine production might well replace the diversion from legitimate production, if any, that now supplies the illicit traffic. The Committee. was unanimous in recommending to the Director 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. Furthermore, countries now using methaqualone for medical purposes should be strongly encouraged to end such use’so as to reduce the need for its legitimate production anywhere in the world. The Committee further recommended that the Director General of WHO should continue to collect data on the use of the drug and to submit it for consideration by the WHO Expert Committee at some future date.
ECDD Recommendation
Placed under surveillance
Link to full TRS
who_trs_775.pdf1.98 MB