The misuse of synthetic psychotropic drugs, as well as of substances such as opiates, cannabis, cocaine and khat, are central to the concerns of the Division of Narcotic Drugs. The question of Catha edulis was first raised at the international level in 1935 at the League of Nations, when the Advisory Committee on the Traffic in Opium and Other Dangerous Drugs discussed two technical papers on this psycho-active plant indigenous to the Horn of Africa.
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Creation Date: 1980/01/01
The misuse of synthetic psychotropic drugs, as well as of substances such as opiates, cannabis, cocaine and khat, are central to the concerns of the Division of Narcotic Drugs. The question of Catha edulis was first raised at the international level in 1935 at the League of Nations, when the Advisory Committee on the Traffic in Opium and Other Dangerous Drugs discussed two technical papers on this psycho-active plant indigenous to the Horn of Africa.
The leaves and young shoots of Catha edulis, a species of the plant family Celastraceae, are usually referred to as khat. Catha edulis grows in eastern Africa and southern Arabia and more specifically in Democratic Yemen, Ethiopia, Kenya, Madagascar, Somalia, the United Republic of Tanzania and the Yemen Arab Republic. Its ecological adaptability, as well as its ability to thrive under a variety of climatic conditions and in various types of soil, facilitates its cultivation in coastal regions and at altitudes from 1,500 to 1,800 metres. Khat users seek out the freshest plant material, usually the leaves and young shoots, which are chewed to permit buccolingual or enteral absorption of soluble ingredients [1] . The pleasurable, stimulating and euphoric effects obtained following absorption of khat constituents are reported to be similar to the effects of amphetamine and its congeners and have been considered as a strong inducement for khat users to procure, by any means, the necessary supplies once a day or more frequently to prolong the periods of chewing [2] . Indeed, such behaviour strongly suggests the development of psychic dependence and is reflected in excessive consumption of khat, with an associated decrease in economic productivity through reduction of working hours because of time spent on chewing khat. In addition, spending on a non-essential commodity at the expense of food has resulted in malnutrition and proneness to disease [1] .
In 1957, international attention was once more directed, through the Commission on Narcotic Drugs, to the nature and extent of the use of khat and to the available chemical and pharmacological data, as well as to the consequences of its use (e.g. mydriasis, elevated blood pressure, hyperthermia, increased respiration, increased sympathetic tone, malnutrition). The World Health Organization (WHO) was also asked to study the medical aspects of khat use and in 1964 the report of this specialized agency was presented to the Commission. However, at that time no action was taken at the international level.
In 1971, the Commission recommended that the United Nations Narcotics Laboratory undertake research on the chemistry of khat and its components. Additionally and simultaneously, WHO was asked to continue its research into the pharmacological action of khat and its effects from the socio-medical aspect. Such research was considered important to provide information needed for the future consideration of possible control measures. In addition, the Laboratory, with the financial assistance of the United Nations Fund for Drug Abuse Control, made a study of the chemical composition of khat using fresh and freeze-dried material from Kenya, Madagascar and the Yemen Arab Republic. Over 20 components were isolated from khat and the chemical structures of most of them were determined. In addition to the isolation and characterization of khat components, the Laboratory also prepared, by isolation and chemical synthesis, adequate amounts of certain constituents of the plant for biochemical and behavioural pharmacology studies to be carried out under the auspices of WHO. The regional offices of this organization in the eastern Mediterranean and Africa have also embarked on an assessment of the public-health and social problems associated with khat chewing.
The principal pharmacological active constituent of khat was previously considered to be cathine ( d-norpseudoephedrine). In 1975, a new compound (alpha-aminopropiophenone) was isolated from fresh khat leaves and its racemic mixture was designated as cathinone. Cathinone is structurally and pharmacologically similar to d-amphetamine, and it has been demonstrated that this constituent of khat produces behavioural effects comparable to those of d-amphetamine. There is evidence that amphetamines produce their pharmacological action by modulating adrenergic/dopaminergic systems at sub-cortical sites; however, it has been suggested that cathinone does not act upon dopamin-ergic systems as d-amphetamine does [3] and is therefore less disruptive to behaviour. These interesting observations require further study and clarification. The stimulant effects of amphetamines and dl-cathinone on the catecholamine systems should be thoroughly examined for regional specificity on brain sub-cortical sites. In addition, the reported euphoric activity should be explored in relation to the actions of other, postulated neuro-transmitter substances in the central nervous system, such as amino acids (e.g. glutamic acid, GABA, kainic acid) and neuro-peptides (e.g. endorphines and substance P), since these substances may have a neuro-modulator effect on drug-induced behavioural responses [4] .
This issue of the Bulletinpresents papers on the chemistry of khat, on cathedulin alkaloids and on the behavioural effects of cathinone. Some of the early literature on the production of khat has also been reviewed and compared with results of a botanical and micromorphological examination of samples of khat recently canqed out at Oslo, Norway. A review of the pharmacology of khat by a WHO advisory group and the conclusions and recommendations of an expert group which met in November 1978 in Madagascar, which also prepared guidelines for future research on Catha edulis, are both presented for the information of the reader. We believe that these presentations will be of value to readers who are interested in and concerned about the abuse of khat.
Catha edulis (khat): some introductory remarks 3
H. Halbach, Problems of Drug Dependence, 1979: Khat - The Problem Today (Rockville, Maryland, National Institute on Drug Abuse, 1980), p.318.
002N. B. Eddy and others, Bulletin of the World Health Organization, vol. 32, 1965, p. 721.
003J. A. Rosecrans, Problems of Drug Dependence, 1979: Discriminative Stimulus and Neurochemical Mechanisms of Cathinone: A Preliminary Study (Rockville, Maryland, National Institute on Drug Abuse, 1980), p. 328.
004V. Singh and G. M. Ling, "Amphetamines in the management of children's hyper-kinesis", Bulletin on Narcotics, vol. 31, Nos. 3 and 4 (1979), p. 87.