Expert Committee on Drugs Liable to Produce Addiction
Pages: 30 to 31
Creation Date: 1955/01/01
The Expert Committee on Drugs Liable to Produce Addiction held its fifth session in Geneva from 11 to 16 October 1954. Its decisions included the following:
The Committee, referring to resolution 548 (XVIII) G of the United Nations Economic .and Social Council on the problem .of diacetylmorphine, pointed out that another country had decided to prohibit the drug's importation as of 1 January 1955, leaving only six countries which have not yet abolished the use of diacetylmorphine. The Committee drew attention to the progress attained within a period of five years towards a recognition of the dispensability of diacetylmorphine and its replaceability.
6 -Methyldihydromorphine and dihydrohydroxymorphinone *
The Committee was of the opinion, referring to the notification of the Government of the United States of' America that these drugs, because they (1) produce morphine-like effects, (2) will suppress abstinence phenomena of a known morphine addiction, and (3) will sustain a morphine addiction, must be considered as addiction-producing drugs comparable to morphine and, consequently, together with their salts, should fall under the regime laid down in the 1931 Convention for the drugs specified in Article 1, paragraph 2, Group I, Sub-group ( a).
The Committee noted further that the evidence accompanying the notification regarding dihydrohydroxymorphinone indicated particularly dangerous addiction-producing properties of this substance and was of the opinion that other less dangerous drugs offer equal therapeutic advantage and emphasized the desirability of avoiding the manufacture, import and export of dihydrohydroxymorphinone.
Myristyl ester of benzylmorphine.
Referring to the notification of the Government of the United State of America, the Committee was of the opinion that there was no evidence that the myristyl ester of benzylmorphine process addiction liability. However, it had information that it can be readily convertible to benzylmorphine or morphine in yields of at least 50 to 60 %.
Retard preparations and mixtures of addiction-producing substances with other agents
The Committee was of the opinion that preparations of morphine in a form that will prolong its effectiveness or the combination of morphine or morphine-like substances with antagonists such as nalorphine to render its use safer, in no way offset the, essential addiction-liability of the morphine or morphine-like components, therefore concluding that such preparations must be handled and controlled exactly as are their, addiction-producing components.
* Dihydro-14-hydroxymorphine is the morphine analogue of dihy-droxycodine. The proposed international non-proprietary name of the latter is "oxycodone".
The Committee took note of a report prepared by the Addiction Research Centre, Public Health Service Hospital, Lexington, Kentucky, U.S.A., with respect to the testing of narcotine for addiction liability. The Committee accepted the evidence in this report and agreed with the conclusion that narcotine .had no addiction liability.
The Committee took note of a report on work m progress to obtain a screening method for determining addiction liability using the monkey as the test subject. It was of the opinion that the results were encouraging towards expediting the classification of addiction-producing agents.
Synthetic substances of methadone type
Referring to the notification of the Government of the United States of America, the Committee was of the opinion that 4,4-diphenyl-6-dimethylamino-3-hexanone (also called "diphenyl-dimethylaminoaethylbutanon "), because it (1) produces morphine-like effects, (2) will suppress abstinence phenomena of a known morphine addiction, and (3) will sustain a morphine addiction, must be considered an addiction-producing, drug comparable to morphine, and that it and its salts should fall under the regime laid down in the 1931 Convention for the drugs specified in Article 1, paragraph 2, Group I.
In the fourth report, its Committee had considered a preparation containing 4,4-diphenyl-6-dimethylamino-3-hexanone and p-oxyphenylmethylaminopropanol. Evidence is now available not only that the components of this mixture, but also the mixture itself, are capable of sustaining an established addiction.
β- 4,4-Diphenyl-6-dimethylamino-3-heptanol( β- methadol)
Referring to the notification of the Government of the United States of America, the Committee concluded that β-4,4-diphenyl-6-dimethylamino-3-heptanol has little or no addiction liability since (1) it has not induced any evidence of morphine-like effect, and (2) it has failed completely to suppressthe abstinence phenomena of a known morphine addiction. Nevertheless, the Committee had specific information that it was readily convertible to acetyl derivatives in good yield, these derivatives having been proved to possess addiction-producing properties. Consequently, the Committee was of the opinion that the convertibility of β-4,4-diphenyl-6-dimethylamino-3-heptanol could be accomplished with such ease and in such yield as to constitute a risk to public health, so that β-4,4-diphenyl-6-dimethylamino-3-heptanol and its salts should fall under the regime laid down in the 1931 Convention for the drugs specified in Article 1, paragraph 2, Group I.
Referring to the notification of the Government of the United Kingdom of Great Britain and Northern Ireland, the Committee noted experimental evidence that 4,4-diphenyl-6-piperidino-3-heptanone has methadone-like properties with respect to addiction potentiality as well as with respect to other morphine-like properties. Consequently, the Committee was of the opinion that 4,4-diphenyl-6-piperidino-3-heptanone must be considered an addiction-producing drug comparable to morphine, and that it and its salts should fall under the regime laid down in the 1931 Convention for the drugs specified in Article 1, paragraph 2, Group I.
Sythetic substances of pethidine type
1-Methyl-4-phenylpiperidine-4-carboxylic acid, isopropyl ester
The Committee, referring to the notifications of the Governments of Italy and the United States of America, took into account the opinion expressed in its first report; namely, that other compounds of a type of structure similar to pethidine and methadone must be under suspicion as to their having addiction-producing properties until the contrary be proved. Accordingly, the isopropyl and other esters of 1-methyl-4-phenylpiperidine-4-carboxylic acid must be suspected of having addiction-producing properties, because general pharmacological experience indicates that in compounds of this type the change from the ethyl to the isopropyl or other ester can effect no significant qualitative changein, and can be expected to effect no major quantitative change in, the action of the compound. Therefore, the Committee was of the opinion that all esters of 1-methyl-4-phenylpiperidine-4-carboxylic acid and theit salts must be considered as addiction-producing drugs comparable to morphine, and that all these esters and their salts should fall under the regime laid down in the 931 Convention for the drugs specified in Article 1, paragraph 2, Group I
Abuse of pethidine among physicians and members of the para-medical professions
The Committee noted the high incidence of such addiction among members of the medical, nursing and associated professions and considered that an important factor in the development of pethidine addiction was the attitude of physicians based on the belief that it is less dangerous than morphine; the Committee, being convinced by experimental and clinical experience with the drug, was of the opinion that pethidine is as dangerous as morphine as a potential addicting agent: it urged the Director-General of WHO to bring to the attention of governments and the medical profession the dangerousness of the addiction, potentiality of pethidine and the needfor the same care in its use as with morphine.
Synthetic. Substances of Azacycloheptane Type.
The Committee took note of a report on a new group of substances of azacycloheptane (hexamethyleneimine) type, which have been shown to exhibit significant analgesic action, but so far have shown no addiction-producing or addiction-sustaining properties.
Synthetic Substances of Other Types
The Committee also noted a report on the development of a new series of compounds of phenylcyclohexane, phenylmorphan, and benzmorphan types. In at least one member of this series analgesic action of an intensity approximately equivalent to that of morphine has been observed. No tests for addiction liability have been made with any member of this series.
The Committee was of the opinion that cannabis abuse comes definitely under the terms of its definition of addiction; that the abuse of cannabis is still a serious problem in many parts of the world; and that not only can there be no abatement in control procedures, but also there should be extension of the effort towards the banishing of cannabis from all legitimate medical practice.