Introduction

 

Khat is usually consumed by chewing the tender leaves and twigs of the plant. The consumption is followed by a feeling of well-being and mental alertness with a sense of disinhibition, excitement and loquacity.

 

The effects of khat and of its major active components, cathinone and cathine, resemble those of amphetamines.

 

Zelger et al. (1), Abdullahi S.Elmi et al. (2), Berardelli et al.(3), Johanson and Schuster (4) and others reported that behavioural effects of cathinone are comparable to those of amphetamines though perhaps quantitatively inferior. Nencini (5) found cathinone lipolytic action similar to that of amphetamines.

 

It has also been shown that cathinone and amphetamine have analogous mechanism of action. Experiments confirming this fact have been reported (6,7).

 

Cathinone injected in rabbits causes a pronounced hyperthermia comparable to that reported for (+)amphetamine (8).

 

Anorexia is associated with khat chewing; still another side effect common with amphetamines.

 

Psychic effects of khat in man mimic those of amphetamines. Mental alertness, increase in motor and speach activity, excitement, weakfulness and disinhibition are produced by both khat and substances of the amphetamine group. Toxic psychosis and aggressive behaviour seen with high doses of amphetamines are, however, very seldom, if ever, seen among khat chewers.

 

The administration of amphetamines enhances athletic performance. This seems to be clear from the literature. Endurance to fatigue in both experimental animals (11, 12) and human subjects (13, 14, 15) have been clearly shown.

 

In the present study pharmacological effects of khat, given orally as water extract or by chewing it, are presented. The main objectives were to get a certain quantification of the effects of khat consumed at rest and to evaluate the influence of khat on physical performance and endurance to fatigue. Among parameters considered are reaction time and cardiac tolerance test.

 

Materials and methods.

 

1. Resting subjects.

 

18 healthy male subjects were chosen among the student population of the university. Their age ranged between 21 to 24 years. They all entered the study voluntarily, without any promise of reward. All subjects abstained from khat for at least one week prior to the experiments.

 

All experiments had been performed under same conditions: same time of the day (starting at 3 p.m.) and after standard diet.

 

The khat consumed by all subjects was of the variety known in Somalia as "harary" and was bought fresh at the khat market in Mogadishu.

 

Each subject chewed one "marduuf" (about 150 g of leaves and tender twigs) in a period of five hours.

 

As is the pattern of khat parties, subjects were sitting all together, on comfortable mattresses with their elbow resting on pillows or leaning against the wall throughout the entire session.

 

The parameters considered were: pulse rate, blood pressure, ECG, rythm alterations of the heart, body temperature, respiratory rate, reflex to light, osteo rendon reflex and reaction time.

 

All determinations except reaction time and osteo tendon reflex were made with subjects lying supine. ECG was carried out with "Cardioline" electrocardiograph. For the assessment of the reaction time an oscilloscope connected to a recorder was used. Three different luminous signals in different order were sent on the panel board of the oscilloscope. Subjects had to press as fast as they could a push-button when one particular signal appeared. The appearance of all signals and the pressing of the buttons were registered by a recorder. The mean of ten answers was considered as reaction time. All participants were trained-, to the exercise before the experiments started.

 

All parameters had been measured 20 minutes before the beginning of khat chewing and 1 and 1/2, three and sixteen hours after. In all tests, control subjects abstained from khat but consumed soft drinks and cigarettes in the same way the khat chewers did. Previous experiments showed that mental and physical effects of khat did not change significantly whether it was used alone or in combination with soft drinks, tea and cigarettes.

 

2. Fatigued subjects - Endurance test

 

14 healthy male subjects were use. The of them participated in previous experiments on resting subjects. Their age ranged between 20 - 24 years.

 

Khat was administered orally and in the form of water extract. The fresh leaves and tender twigs of the plant were finely ground and added with water. The mixture was then warmed up and filtered. Each subject was given the extract of 150 g. The dose produced in all subject typical and strong effects of khat.

 

Subjects were asked to lie down, raise their legs and keep them off the horizontal plane until they were exhausted and unable to keep the position. The exercise was repeated 3 times with intervals of one minute rest, lying supine. The period legs were off the horizontal plane were measured by a stop-watch. The average of the three periods was considered as the time endurance effort.

 

The trials were made 15 minutes before and 1/2, 1 and 3 hours after the administration of khat. Subjects were previously well trained.

 

Cardiac tolerance test.

 

The administered khat was prepared in the same ways as for the endurance test experiment. The 12 subjects used had taken part in either one of the previously described experiments. Each subject was used twice, once receiving khat and not receiving khat on the other occasion. For each subject the two test were done in a weakly interval. Six subjects took part in every session, three receiving the drug and three being used as controls.Seven days later the subjects exchanged parts.

 

The response of the heart to a brief, standard exercise was evaluated. For this purpose a cycle ergometer was used. It was set for a constant load of 1800 g. Subjects attempted to keep to a constant pedalling speed of 60 r.p.m. set by the metronome. Simple electrodes connected to an electrocardiograph (Cardioline) were applied at three surface points at the level of the heart. Heart rate was thus recorded just prior to pedalling and 3 minutes after the beginning of the exercise. The increase in heart rate after the effort was considered.

 

Subjects performed the exercise half an hour before khat administration, at the moment of taking the substance and at half hours intervals after administration for a period of 3 hours.

 

Results.

 

1. Resting subjects.

 

a) Blood pressure: in all subjects an increase of blood pressure was recorded. Systolic pressure rose from the mean basic value of 116 +/- 2.82 to 135 +/- 5,58 after 90 minutes; the highest value of 140 +/- 5.84 was observed after 3 hours, whilst after 16 hours the rate was 116 +/- 3.89.

The trend of the distolic pressure showed an average increase of 67.75 +/- 2.88 before khat consumption to 78.25 +/- 4.18 after one and half hours, 82.75 +/- 3.91 after 3 hours and

70.25 +/- 3.18 after 16 hours.

 

b) Pulse rate: the initial value was 76.1 +/- 4.01. With khat ingestion, a marked tachycardia was recorded in all men. After 90 minutes heart beates were 91.1 +/- 6.57, whilst after 3 hours they were 83 +/- 5.90. After 16 hours pulse rate lowered to 72.6 +/- 3.93.

 

c) Temperature: body temperature too met with increase. Values passed from 36.59 +/- 0.04 before khat ingestion to 37.11 after one and half hour and 3 hours and decreased to 36.07 +/- 0.11 after 16 hours.

 

d) Respiratory rate: also in this parameter there was an increase after khat consumption. The frequency prior to khat was 21.2 +/- 2.57. It rose to a maximum of 28.2 +/- 3.29 after 3 hours and reduced to 19.75 after 16 hours.

 

No alterations regarding the electrocardiograph were recorded. The sizes of P-Q and Q-T intervals remained normal. No alterations of the repolarization phase appeared, nor pathologic rythm abnormalities were detected.

 

We noticed an increase of patellar reflex in 70% of the subjects the reflex to light apparently was not much effected.

 

Reaction time was significantly reduced. In fact from the basic value of 0.3538 sec., it was reduced to 0.262 sec. after 90 minutes and 0.256 after 3 hours. The longest reaction time was recorded after 16 hours, 0.384 second.

 

2. Fatigued subjects:

 

a) Endurance test: It was observed a significant increase in the time subjects kept their legs off the horizontal plane after khat consumption. In fact, before ingesting khat the average time of endurance was 49.6 +/- 7,8 sec. After one hour the endurance time increased to 77.2 +/- 9.8 sec.

 

b) Cardiac tolerance test: The results of this test clearly showed that khat increases pulse rate in resting subjects at the beginning. Than, though other parameters remain high, heart rate decreases. Rate increase after exercise is significantly greater after khat consumption.

 

Discussions and conclusions.

 

In a preliminary study using groups of five students at a time, we detected that the effects of khat are always present and with no significant difference whether it is chewed alone or accompanied by beverages such as tea and/or coke and by cigarettes; the same quantitative and qualitative effects are also obtained whether water extract of khat is administered instead of chewing leaves and twigs.

 

We started than this research in which khat was administered each time in the way most convenient for the experiment in question.

 

Trials to use placebo along with khat chewing have failed since the organoleptic differences were always enough for the subjects to dis tinguish between khat and other products.

 

Our results clearly show that some physiological parameters of the cardiovascular system such as pulse rate, systolic and diastolic blood pressure increase significantly. Effects of khat on these parameters have been reported by some authors (9, 10, 16).

 

The rise of blood pressure reached its maximum 3 hours after the beginning of khat chewing and after 16 hours it was back to normal values. Pulse rate showed maximum increase after 90 minutes and then slowed when the blood pressure was the highest. The same trend has been reported for amphetamines (17).

 

Also the increase in body temperature and respiratory rate is significant

 

The electrical activity of the heart remained within normal ranges, pathologic abnormalities have not been detected by ECG.

 

The nervous system undergoes excitation: patellar reflex and to a lesser extent, reflex to light were enhanced. From the psychic point of vies we noticed an evident state of excitement in all subjects. Khat chewers have the feeling of greater readiness of mind and shortening of reaction time during khat consumption. A decrease in discriminative reaction time with amphetamines has been seen by various authors (18, 19, 20). All cases, but one, in our research showed a reduced reaction time in the drawn experimental model which was discriminative but not complex. The best performance was shown after 90 minutes from the beginning of the chewing.

 

Many authors have shown that amphetamines enhance physical performance and endurance tests (19, 20, 21). Our results point out the similarity of actions between khat and the amphetamines also on resistence to fatigue and physical performance. In fact the duration of adequate performance is prolonged before fatigue appears and the effects of fatigue seem to be at least partially, reversed. Such is also the feeling of the consumers'. Nevertheless, the greater endurance to efforts may be due more to the excitement itself than to a real improvement of working capacity.

 

As shown above, heart rate increases initially with khat and then slows down. In spite of the tendency to restore normal values at rest, the performance of physical exercise causes great increase in rate. The increase- of heart beats is markedly greater with khat administration than without. Fisher (17) obtained similar results with benzedrine.

 

These findings are further evidence of the similarity of action between khat and amphetamines.

 

LITERATURE

 

1. Zelger, J.L. , Schorno, Hj.X. and Carlini, E.A.: Review of the pharmacology of khat" Bull. on Narcotics, XXXII. 3, 67-81,(1980)

2. Abdullahi S. Elmi, Berardelli L., Capocaccia L., Deodati M. and Tancredi V.: EEG and behavioural patterns induced by intraventricular administration of cathinone in rats. Boll. Soc . It . Biol. Sper. LVI. pp 1119-1121, (1980)

3. Berardelli A., Capocaccia L., Pacitti C., Tancredi V.,

Quinteri F. and Abdullahi S. Elmi: Behavioural and EEG effects induced by an amphetamine like substance (cathinone) in rats. Pharmcol.Res.Comm. Vol. 12, 10, pp. 959-964, (1980)

4. Johanson C.E. and Schuster C.R.: A comparison of the behavioural effects of 1- and di-cathinone and d-amphetamine. J.Pharmacol. Ex.Ther. Vol. 219, 2, pp. 355-362 (1981)

5. Nencini P.: Cathinone, active principle of the khat leaf: its effects on "in vivo" and "in vitro" lipolysis. Pharmacol.Res. Comm. Vol. 12, 9, pp. 855-861 (1980)

6. Report of a WHO Advisory Group: "Review of the pharmacology of khat", Bull. on Narcotics, XXXII., 3, pp. 83-93, (1980)

7. Kalix P.: Cathinone, an alkaloid from khat leaves with an amphetamine-like releasing effect. Psychopharmacol. pp. 269 270, (1980)

8. Kalix P.: Hyperthermic response to (-)cathinone, an alkaloid of Catha edulis (khat). J. Pharm.Pharmacol. 32, pp. 662-663, (1980)

9. Halbach, H.: Medical aspects of the chewing of khat leaves. Bu11.W1d.Hlth.Org. 47, pp. 21-29, (1972)

10. Khan, I. and Hughes, P.H.: Assessment of public health and social problems associated with khat chewing. Communication presented to the Annual Meeting of the Committee on Problems of Drug Dependence, Philadelphia, Pa. ,USA (June 1979)

11. Bhagat B. and Wheeler N.: Effect of amphetamine on the swimming endurance of rats. Neuropharmacol. 12, pp. 711-713, (1973)

12. Gerald M.C.: Effects of (+)-amphetamine on the treadmill endurance performance of rats. Neuropharmacol. 17, pp. 703-704, (1978)

13. Cuthbertson D.P. and Knox J.A.C.: The effects of analeptics on fatigued subjects. J.Physiol. 106, pp. 42-58, (1947)

14. Borg, G., Edstrom C.G., Linderholm H. and Marklund G.: Changes in physical performance induced by amphetamine and amobarbital. Amphetamines: medical and physiological studies. pp. 192-200, 1974

15. Smith, G.M. and Beecher, H.K.: "Amphetamine sulphate and athletic performance." J.A.M.A. pp 542-557 (1959)

16. Mancioli, M. and Parrinello A.,: "Il qat (Catha edulis). La Clinica Terapeutica, 43, pp. 103-172, (1967)

17. Fisher J. H . : Cardiovascular effect of benzedrine. Lancet, January 2, 1937. pp. 52.

18. Adler H . F. , Burhardt W . L. , Ivy A. C . , and Atkinson A. J. : Effect of various drugs on psychomotor performance at ground level and at simulated altitudes of 18,000 feet in a low pressure chamber. J.Aviat.Med. 21, pp. 221-236, (1950)

19. Weiss B. and Laties V.G.: Enhancement of human performance by caffeine and the amphetamines. Ann.Rev.Pharmacol. pp. 1-36 (1962)

20. Seashore R.H. and Ivy A.C.: Effects of analeptic drugs in relieving fatigue. Psychol.Monogr. 67, 15, pp. 1-16, (1953)

21. Laties V.G. and Weiss B.: The amphetamine margin in sports. Fed. Proc. 40, 12, pp. 2689-2692, (1981)