Pharmacological Aspects of Chewing the Qat Leaves Part 2 [Archives:2000/35/Health]

archive
August 28 2000

The Effects of Qat Chewing:
During the first part of a qat session, there is an atmosphere of cheerfulness characterized by optimism, high spirits, and a general sense of well-being. The excitement brought out by the consumption of qat reduces social inhibitions and causes loquacity. After 2 hours, a certain degree of tension that reflects emotional instability and irritability becomes apparent. The talking becomes louder, less relevant to the subject under discussion, and there is greater awareness of problems. Later, depressive tendencies appear, and a mood of sluggishness prevails. At this point, the guests leave the qat session with the feeling of depletion.
The desirable effects of qat leaves, as perceived by experienced users, are relief from fatigue, increased alertness and energy levels, feelings of elation, improved ability to communicate, enhance imaginative ability and capacity to associate ideas, an heightened self confidence. These effects seem to be more readily perceived by the habitual user. Since the social environment in which the drug is consumed appears to play a role in the response, it is important to take into account not only the effects of qat itself, but those of the qat session as well. It is of interest that the response appears also to be influenced by conditioning, since in Djibouti, where qat is flown in daily, it is commonly said that the effects of the drug begin when the incoming plane is heard in the sky.
The objectively observable effects of qat use consist of mild euphoria and excitement accompanied by episodes of logorrhea and then verbal aggressively. There is also an increased sensitivity to sensory stimulation; excessive qat use may cause hyperesthesia. Hyperactivity may be observed and the associated behavioral syndrome can be described as hypothemania; a manifestation of irresponsible fearlessness has also been reported. In exceptional cases, qat consumption may produce an immediate dysphoric reaction which might, however, be due to excessive expectations with regard to potency of a given batch of qat. The late effects of qat use are mainly an inability to concentrate, and insomnia. It is important to note that high doses of qat or exceptionally potent material can induce psychosis, presumably by enhancing a subecute prepsychotic or psychopathic condition. However, such symptoms are mentioned only occasionally in literature, probably because in many cases they are considered as being at the extreme limit of normal behavior. Nevertheless, a number of case reports on qat-induce toxic psychosis have appeared. The usefulness of phenothiazines for reducing the central nervous system (CNS) toxicity of qat was reported some time ago; at present, thioridazine is suggested for the symptomatic treatment of qat psychosis. Impairment of mental health may also be the result of long-term qat consumption; long-term chronic users may develop personality disorders and suffer mental deterioration.
The symptoms described above, particularly that of toxic psychosis are reminiscent of those induced by amphetamine. Similarity of effects of the two drugs has already been reported, and it has been concluded that the differences between the effects are essentially quantitative. Indeed, Hughes has stated from personal experience that the effect of a portion of qat is very similar to that of about 5 mg of amphetamine. A further analogy with amphetamine is that the habitual use of qat is in many instances compulsive, as indicated by the tendency of the chewers to secure their daily supply of the leaves at the expense of vital needs. Drug dependence of the qat type has been described by Eddy et al., and it appears that its only major difference from amphetamine-type dependence is the physical impossibility of increasing the ingested dose beyond a certain limit. This probably explains why tolerance to the physical to the psychostimulant effect of qat has not as yet bee observed. Similarly, no clear abstinence has been found to occur after prolonged qat use, although a mild depressive reaction during withdrawal from qat is sometimes seen. Any definitive investigation of tolerance or with drawl symptoms would, however,, require a thorough clinical study involving monitoring of the blood levels of the active qat constituents.
An important effect of qat, the induction of anorexia, was already reported in the early Arab literature. This anorexia, along with the tendency of habitual qat users to divert their funds from food to qat, would account for the generally observed malnutrition which predisposes the users to disease. Ingestion of the leaves seems to have no effect on the blood level of glucose. On the other hand, qat has been reported to cause an increase in respiration and induction of hyperthermia; a case of lethal hyperthermia following qat consumption has been described.
Consumption of qat, like that of amphetamine, causes a number of sympathomimetic effects. At the cardiovascular level, there are arrhythmias and an increase in blood pressure depending on the amount and potency of the material absorbed. The cardiovascular response to physical effort is exaggerated. Acute cardiovascular problems, particularly in older people, have been reported. Habitual use of qat may lead to chronic hypertension which, upon abstinence from the drug, can change into a transient hypotensive state. A further sympathomimetic reaction to qat use is mydriasis. qat chewing is known to seriously impair male sexual function and to lead to a high incidence of spermatorrhea which is sometimes accompanied by testicular pain. Long-term chronic use may lead to permanent impotence.
Dryness of the mouth is commonly, felt during qat chewing, and this may be explained either by the sympathomimetic effect of the drug or by its astringent taste. Sine qat leaves have a high tannin content, qat chewing frequently causes periodontal disease, mucosal lesions, and a number of irritative disorders of the upper gastrointestinal tract. The polyphenolic tannin compounds in qat can also be presumed to increase the probability of oesophageal cancer. In an epidemiological field study in Yemen, Kennedy et al., while having the general opinion that the role of qat in the health problems of that country has been highly exaggerated, have nevertheless confirmed the high incidence of gastrointestinal problems in qat users. {In animal experiments, gastritis and duodenitis have been provoked by adding qat of qat extracts to the food pellets of rats; on the other hand, inclusion of qat in rat standard diet has been reported to prevent the induction of gastric mucosal damage by phenylbutanoze, an effect tentatively attributed to the flavonoids present in the leaves.} A common ailment of qat users is constipation, probably caused by the astringent properties of qat tannins. Habitual users try to attenuate this undesirable effect by food adaptation, notably by eating, prior to the qat session, a meal with high fat content in order to facilitate intestinal transit.
Due to the fact that the leaves are a non-standardized material , the potency of which may vary considerably from batch to batch, it is difficult to make a quantitative evaluation of the effect of qat use. A further problem for clinical studies is the impossibility of replacing the active drug with an indistinguishable placebo. In addition, there are certainly large inter-individual variations in the mastication efficiency and in the absorption of the active ingredients. Although there is, at present no study that allows the determination of serum concentrations of active qat constituents, an attempt has been made to determine the effects of qat on several clinic parameters (body temperature, respiratory rate, pulse rate and blood pressure) in habitual users, on the one to hand, and on subjects unaccustomed to qat chewing , on the other. The qat-induced changes appeared to be less pronounced in chronic users, which would indicate that tolerance may develop to the sympathomimetic effects of qat. In a short report by the same authors ), qat chewing is described as causing the same modifications of the plasma levels of somatotropic and adreocorticotropic hormones as amphetamine.
The mutagenic potential of qat has been estimated in an animal study, in which qat extracts were administered to rats; unfortunately, the i.v. instead of the intragastric route of administration was chosen for these experiments. Under these conditions, the extracts were found to reduce nucleic acid synthesis in brain and liver, and to produce chromosomal abnormalities in bone marrow.

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