QAT: A Dangerous Drug Under the Microscope [Archives:2000/02/Culture]

January 10 2000

1st in a Series
1 of 9 (1990)
TL {Qat Ða dangerous drug ?}
AU: Kalix- P
SO: Harefuah. 1990 May 1; 118 (9): 555-6
TL: The induction of dominant lethal mutations upon chronic administration of Qat
( Catha edulis ) in albino mice.
AU: Tariq- M; Qureshi- S; Ageel- Meshal- 1A
SO: Toxicol- Lett. 1990 Feb; 50 (2-3): 349- 53
AB: The mautagenicity of a methanolic extract of Qat has been evaluated on male germ cells using the dominant lethal test in albino mice. An aqueous solution of Qat extract was administrated orally in doses of 50, 100 and 200 mg/kg body wt., respectively, to 3 different groups of male mice for a period of 6 weeks. At the end of treatment each male mouse was allowed to mate with 2 different groups of 3 females each, on 2 consecutive weeks. These females were necropsied on the 13th day of their presumptive mating, and the number of implants in each female and the ratio of live and dead embryos were determined. The results of this study showed that the treatment of male mice over a period of 6 weeks produced a dose-dependent reduction in the rate of fertility in the first week after mating, which was irreversible in the second week at the highest dose (200 mg/kg ). Qat extract also induced post implantation loss during the first weeks showed a reversible pattern of dominant lethality.
3 of 9
TL: An evaluation of the male reproductive toxicity of cathinone.
AU: Islam-MW; Tariq-M; Ageel-AM; el-Feraly- FS; al Meshal- IA; Ashraf-I.
SO: Toxicology. 1990 Mar. 16; (3): 223-34
AB: (-)- Cathinone is the major psychoactive component of Qat plant ) Catha edulis Forssk). Qat has been shown to produce reproductive toxicity in human beings and experimental animals. However, the chemical constituents of Qat leaves responsible for sexual dysfunction are not known. In the present study cathinone enantiomers have been investigated for their reproductive toxicity in rats. Cathinone produced a dose-dependent decrease in food consumption and suppressed the gain in body weight. There was a significance decrease in sperm court and motility and increase in the number of abnormal sperms in cathinone treated animals. Histopathological examination of tests revealed degeneration of interstitial tissue, cellular infiltration and atrophy of Sertoli and Leydig’s cells in cathinone treated animals. Cathinone also produced a significant decrease in plasma testosterone levels of the rats. Although both enantiomers of cathinone produced deleterious effects on male reproductive system, (-) cathinone was found to be more toxic. From this study it may be concluded that the cathinone content in Qat may be partially or totally responsible for the reproductive toxicity in Qat chewers.
4 of 9
TL: Pharmacological properties of the Qat
AU: Kalix- P
SO: Pharmacol- Ther. 1990; 397- 416
AB: The chewing of the stimulant leaf Qat is a habit that is widespread in certain countries of East Africa and the Arabian peninsula. During the last decade, important progress has been made in understanding the pharmacological basis for the effects of Qat. It is now known that the CNS action of this drug is due to the presence of the alkaloid cathinone, and the results of various in virto and in vivo experiments indicate that this substance review of describe briefly the Qat habit and to summarize the pharmacology of Qat and of its active constituents.
5 of 9
TI: Dopaminergic nature of acute cathine tolerance.
AU: Schechter- MD
SO: Pharmacol -Biochem -Behav. 1990 Aug; 36 ( 4): 817- 20
AB: cathine is a psychoactive constituent in the leaves of the Qat shrub which are habitually ingested for their stimulatory in many parts of the world. Rats were trained to discriminate the stimulus effect of intrperitoneally administered 4.8 mg/kg d- cathine and once trained, administration of another Qat constituent, cathinone, -was shown to produce cathine-like effects. This generalization to cathinone was dose responsive when testing occurred 24 hr after vehicle administration, whereas prior administration of cathine resulted in a diminished discriminative response to subsequent cathinone administration possibly as a result of the development of acute tolerance. CGS 10746B, a compound that blocks presynaptic release of dopamine, significantly decreased rats’ ability to discriminate cathine when it was administered 25 min prior to cathine testing and it reversed the acute tolerance observed when cathine was tested 24 hr after cathine administration. These results indicate that a previously -reported acute tolerance effect to cathine after cathinone administration in cathinone trained rats appears to be symmetrical in that there is acute tolerance to cathinone after cathine in these cathine-induced rats. The results with CGS 10746B would suggest that both the cathine-induced discriminative cue and cathine’s ability to produce acute tolerance are mediated by presynaptic dopamine release.
6 of 9
TI: Effects of cathinone and amphetamine on the neurochemistry of dopmine in vivo
AU: Pehek- EA; Schechter-MD; Yamamoto -BK
SO: Neuropharmacology. 1990 Dec; 29 ( 12): 1171-6
AB: The effects of (-) cathinone, the primary alkaloid of the Qat plant, were compared to those of (+) amphetamine in the anterior caudate-putamen and the nucleus accumbens. In vivo microdialysis was used to measure extracellular levels of dopamine and metabolities in both regions of the brain simultaneously, after intraperitoneal administration of 0.8, 1.6 or 3.2 mg/kg of either drug ( doses expressed as the salts ). Both drugs increased levels of dopamine but decreased levels of metabolites in a dose-dependent manner. However, the relative magnitude of these effects dependent upon the specific drug, the dose and area of the brain examined. At the largest dose used, amphetamine had a relatively greater effect than cathinone on dopamine in both caudate and accumbens. However, among smaller doses, this difference was only observed in the nucleus accumbens after administration of 1.6 mg/ kg. The results also demonstrated a differential regional effect of both drugs at 3.2mg/kg in that both had a greater effect on dopamine in the caudate, as opposed to the accumbens. These findings demonstrate a functional heterogeneity of the striatum of the rat, that may be relevant to the understanding of both normal brain function and the neural responses to psychoactive drugs.
7 of 9
TI: Amphetamine- like effect in humans of the Qat alkaloid cathinone
AU: Brenneisen-R; Fisch-HU; Koelbing-U; Geisshusler-S; Kalix-P
SO: Br-J-Clin-pharmacol. 1990 Dec; 30 (6): 825-5-8
AB: 1. The chewing of Qat leaves as a sttimulant is common in certain countries, and the effects of this material are supposed to be due to the phenylalkylamine alkaloid cathinone. In order to determine the effects of this sustained to six healthy male volunteers in a double-blind, random order crossover study. 2. Cathinone produced increases in blood pressure and in heart rate, and these changes were concomitant with the presence of cathinone in blood plasma. 3. The physical and mental changes that the subjects reported during the experiment indicated that cathinone has in humans euphorigenic and psychostimulant effect. 4. These observations support the assumption that cathinone is the constituent mainly responsible for the effects of Qat, and they show that this alkaloid has also in humans amphetamine-like effect.
8 of 9
TI: Effect of Qatamines and their enantiomers on plasma triiodothyonine and thyroxine levels in normal Wistar rats.
AU: Isalm -MV; Tariq -M; el-Ferarly-FS; al-Meshal- IA
SO: Am-j- Chain -Med. 1990; 18 (1-2): 71-6
AB: The effect of cathine and N-formylorephedrine, two psychoactive amines of triiodothyronine (T3) and thyroxine (T4) in male Wistar rats. The rats were injected with 5, 10 and 30 mg/kg, body weight of four Qatmines and the blood samples were collected 2hr after their administration . in the separate set of experiments the effect of these Qatamine failed to produce a significant dose dependent increase in T3 and T4 levels in the dose of 5 mg/kg. However, all of these compounds produced a significant dose dependent increase in T3 and T4 levels at higher doses but only T4 levels were increased following the dose of 10 mg/kg. Our studies on the effect of Qatamines in T3 and T4 levels at various times showed a significant increase in T4 levels in all the four groups treated with various Qatamines and the peak effect was observed at 2 hr in case of (-) and (+) cathinone and 4hr in case of (-) and (+) N- formylnorephedrine. This study suggests that the symptoms observed in Qat chewers including hyperthermia, and metabolic changes may to some extent be attributed to the thyroid hormones by these compounds and their involvement in the pharmacological effect.
9 of 9
TI: Discriminative stimulus properties of ( +) cathine, an alkaloid of the Qat plant.
AU: Pehek- EA; Schechter- MD
SO: Pharmacol- Biochem-Behav. 1990 Jun; 36 (2): 267-71
AB: The effects of the psychostimulant (+) cathine ( norpseudoephedrine) were examined in a two-choice, food-motivated, drug -discrimination paradigm. Rats were able to discriminate cathine from vehicle and this effect was dose – and time dependent. Prior administration of cathine resulted in a diminished response (tolerate) to subsequent cathine and this effect developed and dissipated rapidly. Thus, different dose-response curves were generated depending upon whether cathine or vehicle was administered the day before testing. The development of tolerance also shorted cathine’s time course of action and enhanced the ability of haloperidol to antagonize the cathine cue. These result cautionin interpreting effects produced by intermittent drug injection schedules.
1 of 9 (1991)
TI: Catha edulis international socio-medical problem with considerable pharmacological implications.
AU: Balint-GA, Ghebrekidan-H; Balint- EE
SO: East- Afr- Med-J. 1991 Jul; 68(7): 555-61
AB: It is evident from the mentioned studies that the medical and psychosocial effects of Qat chewing are hazardous both to the psychoeconomic structure of the subject. Being aware of the increasing prevalence of Qat chewing (often together with other drugs), it is essential to assess the health and socio-economic problems of Qat habituation in order to take further, appropriate medical and social measures.
2 of 9
TI: Qat and oral cancer.
AU: Soufi-HE; Kameswaran- M; Malatani- T
SO: J-Laryngol- Otol. 1991 Aug; 105 (8): 643-5
AB: Oral cancers in the Asir region of Saudi Arabia have been observed to occur mostly among patients who have been long-term Qat users. In a survey that reviewed cancers for the past two years there were 28 head and neck cancer patients, 10 of whom presented cervical lymph node and unknown primary, one was a parotid tumour, and the remaining eight presented with oral cancers. All were non-smoking Qat chewers and all of them had used it over a period of 25 years or longer. We conclude that this strong correlation between Qat chewing and oral cancer warrants attention.
3 of 9
TI: The toxicity of Catha edulis (Qat) in mice.
AU: al-Meshal- IA; Qureshi- S; Ageel- AM; Tariq-M
SO: J- Subset-Abuse. 1991; 3(1)” 107-15
AB: A large number of people in East Africa and Southern Africa chew Qat leaves because of its pleasurable and stimulating effects. Due to its habit forming property, the Qat has been classified as a “Substance of Abuse” by the World Health Organization. In view of the large number of medical problems reported in Qat chewers, the present study was undertaken to investigate the chronic toxicity of Qat extract in the dose of 50, 100, and 200 mg/kg. Body weight daily by oral intubation route for 6 weeks. The results indicated a dose-dependent decrease in body weight, an increase in the lymphoid tissues. The necrotic areas in the subcutaneous tissues showed the presence of numerous polymorphs.
4 of 9
TI: {Qat, a herbal drug with amphetamine properties }
AU: Kalix-P; Brenneisen -R; Koelbing -U; Fisch- HU; Mathys-K
SO: Scweiz -Med- Wochenschr. 1991 Oct 26; 121(43): 1561-6
AB: Because of their stimulating effect, leaves of the Qat bush are chewed in several East Africa countries and in Yemen since only fresh leaves are active, this habit is almost unknown outside the regions where the plant grows. Recently, however, Qat has made its appearance in the United States of America and several European countries, while an import permit has been requested in Switzerland, these are reasons for making the practitioner familiar with the effects of this drug. During the last fifteen years, knowledge of Qat and its constituents has made substantial progress. Today, the alkaloid cathinone is regarded as the main active principle of this drug, and this substantial is held to be a natural amphetamine. This article summarizes knowledge of the pharmacology of Qat.
5 of 9
TI: Effect of repeated administration upon cathinone discrimination and conditioned place preference.
AU: Schechter- MD; McBurney-D
SO: Gen-Pharmacol. 1991; 22 (5): 779-82
AB: 1. Eight male rats were trained to discriminate the interceptive cues produced by 0.8 mg/kg 1- cathinone in a two-lever, food-motivated operant task and they were, subsequently, tested for preference to cathinone in a conditioned place preference (CCP)-test. 2. Once trained, the rats were placed on a 10 day regimen of multiple injections of 0.8 mg/kg cathinone. 3. After each series of non-contingent administrations, the rats’ ability to discriminate (0.2-0.8 mg/kg) cathinone, as well as their preference for it, was determined. 4 Results indicate that tolerance tends to develop to the effect of cathinone in its ability to control discriminative behavior as indicated by deficit in discriminative performance and a two-fold shift of the dose response curve to the right. 5. In contrast, preference for cathinone, in the CPP-tests, was not significantly affected by the multiple cathinone administration regimen. 6. The possibility that tolerance to some behavioral effects may occur in habitual users of the cathinone-containing Qat shrub is discussed.
6 of 9
TI: The pharmacology of psychoactive alkaloids from ephedra and catha.
AU: Kalix- P
SO: J-Ethnopharmacol. 1991 Apr; 32 (1-3): 201-8
AB: Ever since the introduction of the alkaloid ephedrine as an anti-astimatic, the CNS stimulatory effects of this sympathomimetic have been problem in therapy. Indeed, the use of ephedrine is not only limited by its cardiovascular effect has recently received renewed attention. Besides ephedrine, the ephedra plant contains some norpseudoephedrine. This substance is also called cathine, because it is a major alkaloid of Catha edulis, or Qat, a plant that is widely used as a stimulant in certain countries of East Africa and of the Arab Peninsula. The effects of Qat have been explained formerly by those of cathine; some time ago, however, the labile alkaloid cathinone was discovered in Qat. This substance is the keto-analog of cathine; it is therefore more lipophilic and penetrates easily to its sites of action in the central nervous system. Indeed, cathinone has been found to be a highly potent CNS stimulant and it is now known to be the main psychoactive constituent of Qat; the results of various in vitro studies indicate that cathinone must be considered a natural amphetamine. In confirmation of this view, it has recently been demonstrated that has in humans marked euphorigenic and psychostimulant effects. As the case may be, these findings may lead, together with epidemiological data, to a reconsideration of the use of Qat as a stimulant and social drug.
7 of 9
TI: Cathinone, a phenylpropylamine alkaloid from Qat that has amphetamine effects in humans.
AU: Kalix-P; Geisshusler-S; Brenneisen-R; Koelbing-U; Fisch-HU
SO: NIDA-A- Res- Monoger. 1991; 105: 289-90
8 of 9
TI: Cerebral function of the guinea pig neonate after chronic intrauterine exposure to Qat ( Catha edulis Forsk).
AU: Thordstein-M; Jansson- T; Kristiansson-B
SO: Biol-Neonate. 1991; 59(3): 161-70
AB: Cerebral function in normoxia and its reactions to standard periods of hypoxia of increasing severity were studied in 30 newborn guinea pigs less than 3 days old. Intrauterine growth retardation was induced either by uterine artery legation at midgestation or by feeding the female in late gestation with Qat leaves, an amphestation-like stimulant chewed by men and women in several countries in Eastern Africa and Arabia. After spontaneous delivery, the neonates were anesthetized and ventilated. Cardiovascular, metabolic, and neurophysiolgic (somatosensory evoked potentials) parameters were monitored. Under normoxia, the Qat-exposed group showed prolonged latency of the primary response of the somatosensory evoked potentials and a reduced amount of secondary components. Under hypoxia, this group also has a greater reduction of amplitude of the somatosensory evoked potentials. It is concluded that Qat exposure during fetal life gas an impact on the cerebral function during the neonatal period (at least up to 3 days of age ) which is not solely explained by the concomitantly produced growth retardation.
9 of 9
TI: Qat-chewing during pregnancy-effect upon the off-spring and some characteristics of the chewers.
AU: Eriksson-M; Ghani-NA; Kristiansson-B
SO: East-Africa _Med-J. 1991 Feb; 68 (2): 106-11
AB: IN a study of 1, 141 consecutive deliveries at delivery centers in the Yemen Arab Republic, the effect of Qat (catha edulis) upon the offspring have been studied. The leaves of the shrub Qat contain euphorizing compounds and are chewed often, even daily, by many inhabitants. Non-users of Qat (n= 391). The Qat-chewing mother was older, of greater parity and had more surviving children than the non-chewers. Significantly, more Qat- chewers had concomitant diseases. There was no difference in rats of stillbirth or congenital malformations.
1 of 4 (1992)
TI: Treatment of Qat addiction.
AU: Giannini- AJ; Miller-NS; Turner-CE
SO: J-Subst-Abuse-Treat. 1992 Fall, 9(4): 379-82
AB: The authors present two cases of Qat addiction that were successfully treated with bromocriptine. Qat is a bush cultivated in the Mid East because of its highly stimulant effects. Its leaves contain a variety of sympathomimetics. While Qat is rarely found in the U.S., America soldiers stationed in the Arabian peninsula may be exposed to it. Because of an alcohol interdiction during the current Persia Gulf crisis, these troops may be tempted to use this plant as an alternative recreational drug.
2 of 4
TI: {Qat-a new drug in Finland}
AU: Tacke-U; Malinen-H; Pitkanen-H
SO: Duodecim. 1992; 108 (16): 1390-4
3 of 4
TI: Increases in the locomotion of rats after intracerebral administration of cathinone.
AU: Calcagnetti- DJ; Schechter-MD
SO: Brain -Res-Bull. 1992 Dec; 29 (6): 843-6
AB: There is a widespread practice among people living in Eastern Africa and Southern Arabia of chewing the leaves of the Qat shrub so as to produce pharmacological effects that ate practically indistinguishable from those produced by amphetamine (AMPH). Cathinone (CATH) has been identified as the psychostimulant constituent of this plant and, although the locomotion elevating effects of centrally administered AMPH and cocaine (COC) in rats are well known, there is a paucity of dats regarding CATH. Three experiments were, therefore, conducted to measure locomotor activity following central administration of CATH in rats. The first experiment determined the dose-dependent effects of CATH activity following intracerebroventricular (ICV) administration. As psychostimulant effects are believed, at least in part, to be mediated by dopaminergic systems, in Experiment 2 CATH was injected into the dopamine nerve terminal of the nucleus accumbens. Experiment 3 examined the effects of CATH injection into the dopamine cell body region of CATH revealed a dose-dependent increase of activity. the highest dose tested (64 micrograms) yielded a 114 % increase in activity when compared to baseline, whereas a 20 micrograms bilateral nucleus accumbens (NA) injection of CATH increased activity fivefold. These findings evidence the hypothesis that the effects of CATH are dopaminergically mediated. Substantia nigra (SN) injections
4 of 4
TI: Cathinone, a natural amphetamine.
AU: Kaix- P
SO: Pharmacol- Toxicol. 1992 Feb; 70(2): 77-86
AB: Cathinone is an alkaloid that has been discovered some fifteen years ago in the leaves of the Qat bush. This plant grows in East Africa and in Southern Arabia, and the inhabitants of these regions frequently chew Qat because of its stimulating properties. Cathinone, which is S (-) -alpha-aminopropiophenone, was soon found to have a pharmacological profile closely resembling that of amphomimetic effects; thus, for example, drug-conditioned animals will not distinguished between cathinone and amphetamine. These various observations were confirmed by a clinical experiment showing that cathinone also in humans produces amphetamines-like objective and subjective effects. Finally, it was demonstrated that cathinone operates through the same mechanism as amphetamine, i.e. it acts by releasing catecholamines from presynaptic storage sites. Thus, much experimental evidence indicates that cathinone is the main psychoactive constituent of the Qat and that in fact, this alkaloid is a natural amphetamine.
To be continued next week…