| dc.description.abstract | Forsk, also known as Miraa, grows in the Eastern part
of the African corrt inent from Ethiopia to South Africa. The young twigs
of this p'larrb are nnsticated to give a central stimulant effect. The leaves,
.shcct.s and roots have also been used in herbal rredicine pre par-atrlons ,
The central stimulant effect of X.?tq§. eduli~ has been known for a
long time. However, details of its discovery Ia ve been lost in legends
ani obscuri ty • Till first reference to the use of Catha edulis was in a
prescription by Naguib Ad-Din in 1237 A.D. Later, there were nurrerous
references to it especially in the fourteenth Century be cams known in Europe the writings of Vaugham
who was a Port Surgeon at Aden in the 1850s. The medicosooio.l repercussions
arising from the inliscriminate use of Q.~tha rm.terial in Arabia and Eastern
Africa were generally VIS 11 recognised by the beginning of the 20th Century.
For examp.le, contro 1 treasure s were enacted in 1921 and 1939 by the British
Colonial Government, in vtJ.at was then British Sorm.liland and Kenya Colony
respccti ve lYe
Till first concerted effort to control the indiscriminate use of Q.aj;h§-.
rm.terial was rrade in 1956 when the United Nat io ns Drug Commission at the
request of the Arab League considered the problem posed by the excessive
use of ~tllD. rmterial. Shortly afterwards, the United Nations Economic
and Social Commission re quested the Ylorld Health Organisation to study
till medical aspects of the consumption 0 f Q..aA~2.£.tllis. Since then, publications
on vch e effect of chewing £Laj;hannterial have increased considerably,
but not much definite and authoritative docunerrtat.Lon exists about its
toxicity. It was in recognition of this fact that the present study vvas
urdorrt aken to provide additional valuable and comprehensive Lnf'or-nat Lon on
all aspects of ~h~ £Aul~ toxicosis.
Toxicology is not a distinot discipline in its own right. It is a
hybrid of n:any disciplines, among them chemistry, pharrracoLogy, psychi.at.r-y,
pathology, physiology, and biocherillBtry. A taKicological study of any
problem is, therefore, bound to bo biased depend.Lng on till specific interest
of the research worker. Till present study is a compranise of nany interests
all aimed at providing as much inforIlBtion as possible on the toxicity of
Q.atdl.2.. nat erial •
Till impetus for research on C_athQ.nat.erd al, t oxtcosi s waS a recognition
of possible barmful effects in t110se people VIDO indulge in excessive chewing
of the nabcr-Lal,, For example, there has been sps cuLet.Lonthat Q,g,th:tnaberd.a.L
mid1t be a contribut ory factor in tho aetiology- of oesophageal cancer and
in cirrhosis of the liver.
Prior to starting the experimental work, a survey was carried out "!lith
a view to obtaining a basis for experd merrba.L work and also to ascertain or
refute certain empirical information that m'8 quoted ~reely in literaturo.
During t.le survey of literature, it became evident that there still
exists a controversy as to wheth er there are more than one aLka LoLd in ~'~'la
nater-Lal., It Vias, therefore, decided to investigate this aspect of the
problem using chr-omatographic and SIB c'tz-ophot onrrtz-dc teclmiques.
Q.atbg,rmterial was incorporated into food in concentration of 1, 5, 10,
15, 25 and ffJ}~and fed to woanling rats 34 weeks old. The rats were observed
for bebavioural changes and for general signs of toxicity. The toxicity of
C~Jh.~IIR ter.:i.al in rats was also evaluated by its effect on th e growth rate,
symptomatology, change in organ-body v/eight ratios, gross pathology ani
histopathology. Rats feeding on various concentrations of .Q§:cl;¥!. I1Bterial
(extract or non-extracted) were sacrificed at different exper-LmerratL stages
and examined for gross and hi.ct opath o'l.oglcaL lesions.
TlB transmission of the tcoci..cprinciple(s) of 9_atha material through
the placental tissue and mammar-yglands was evaluated by gross and histopathology
of yotmg rats irrmediately after birth and of sucklings approxilIRtely
nine days after birth respectively.
Rats fed 5, 10, 15 am 28'/0 ~tha extract for more than 3 months were
mated using male rats fed a corresponding percentage of Cat,'1.§n!.at.er-La'Land
the rew horn examined for morphological deformities immediately after birth.
Tre average "Fleight and number in each littor was recordod and tho data
from ten litters anaLysed and compared vrith that of control rats. Approxirru:~
tely ore rn Lf of tre litter was left to grow and examined for any
deformities tilat might not !r.ve been detected at birth.
Rabbi.t.a we.re also fed Q.9.thamat.erd.aL extract in tre concentration of
15 and 28,Po and their blood pressure determined, using Grants ear capsule
method. Similarly, daily excretions of Na+ and K+ were det.er-m.i.ned, .4.fter
about fohr months, blood was obtained from rabbits and examined for haennt.ological
and biochemical changes.
The pharrmcoLogy of th e activ,e principle of Qi;.th§;.material was studi ed,
the ernplnsis be ing on those aape ct s which rela te to tho toxicity of Q.;.'1:.t,lp.
na+erd a'l , In r,nrticul...'1r, the effect on the smooth muscles (GIT,trachoa,
uterus), tho cardiovascular system (heart and peripheral blood vessels)
am central nervous system was ccnsidered important in this respect.
Results of the survey LrdLc.rted that the active principle present
in 9.~tl£ material is a psychotropic compoundwhich also induces s one
hallucinations. Tre effect is biphasic, the first phase is one of stimulation,
and this is followed by the second phase of depression. Tre offect
on sexual behaviour closely follows that of the c ent ra.L nervous system,
i.e. intial stimulation follovred by depression.
TlE survey also showed thc1t people who indulge in excessive chewin:g
of Q..§ltpE.material develop a form of dopondence which was considered "habituati
ve" rathe r than "addictive". Till precise ccntribution of 9.atha rraterial
to the overall health of th e individuals was uncertain but it appeared to
vary considerably I dependdng on the f.:::eding habi,ts. 'I'be possible contriliution
of Catha material to schizop.h:oonia was considered minimal. It was noted tlll:1t
several non-Mos Lemswho chew9.a..t..h£. nnterial also smoke bhang and indulge in
heavy drinldng. In nearly a 11 cases, those vtlo crew C.at49-1llE.terial (but do
not drink or- smoke bhang) were found to be gererally calm, withdravm ani
+erd ed to avoid noisy places. This finding is in sharp contradicti on to
published reports, mostly by non-Africans, which tend to portray those who
cp..ewQ..at~.l1lllterial as being "quarr-e.Lsona and ant.agorri st.Lc'' to all forms of
authority and generally as being "predisposed to maniacal outburst".
Cremical analysis of Cath.'1.material showed that there is only one
alkaloid, d-norpseudoephedrine. It was pre sent in all parts of the plant
examined.
Feeding rats on Q,.c;,tharraterial caused retardation in growth oven when
no significant gross or histopathological Lesxo ns were noted. 'I'Iere was an
irrlication of development of tolerance wi.t h respect to inappetite and central
nervous system effects in rats fed ~tlE material extract.
Tte most consistent finding in rats fed high concentrotions of QI';.il.1~
nnt orti nL was extensive deaquannt ion and ulceration, sonet ina a haemorr-bagi c,
especially in -che st onnch, and duodenum. Catha rrnterial extract incorDo- _ _ 6
rated in food caused little or no bT03S or histopathologic~l lesions as
compar-edto the bu'Lky , non-extracted Cg,thq material Lncoz-por-at.edin food.
It appear-ed that the difference could partly be accounted for in terms of
effective contact between the toxic nnterial and the glnndulnr mucosal
epi t.heLl.um, This is consistent with int'orrrntion gained during the survey
which indi cat.ed that th e st cmachdiscomfort exper-i.enced by Mlz-aachewers
was especially mar-kedwhen the material vras ingested before eating food.
Centrolobular mcrosis in hepatic lobules and coagulative necrosis of
reml cor-tex were observed in t re liver and kidney re spectively associated
I'dth ulcera-tion 0 f gastrointestiml tract (GIT). Sorre rats which apparently
died suddenly - and whi.ch showed haemcrr-hagi.c ulceration in the GIT had no
lesions in the liver and kidney. Trese lesions -were directly attributed to
tannins and it appeared -!:;hat tho tarmins first impaired the integrity of
mucosal epitlBlium ard wer-e subsequently absorbed into the body where they
caused lesions.
CoaguLatzlve necrosis was observed in the heart of rats fed both the
extract and the non-extracted Q.atl:§.material. Although trese lesions wer-e
observed in appr-oxi.nntely 30%of rats fed 25 and 5CJfo Q..atln.matertl o.L, S 01lE
significance was attached to this finding because of SOlID published work
vbich shows that sevoral sympathomimetic anri nos can cau se similm- lesions.
Results obtained vdth rabbits were generally in agreement with thoso
obtcinod with rats in r-e sps c't to gross and histopathology of various organs.
Trere W[tS no finding to implicate 8tr"t.he. mo.terial in malignant growth as has
been speculated by some research wor-knr-s , Do-gene·rative changes (vacuolation,
cloudy swelling etc ) of vo.rying degree and exterrt were fre quently observed in
both rats and rabbits f'ed Q..atjmmaterial extract or low cancentraion of
whole Q..atha na berd.al, and also in some control rats. Interpretation of
degererati ve changes is often difficult e spacd.aLl.y where there is no progressive
involvement of th e tissue with time. For example, a disturbance in
tm oxygen or nutrition re qut.r-ene rrt of the tissue, even for a short tirro,
will often Le ad. to degenera ti ve chan {§3 s •
The pbaz-nnc oLogy of d-norpseudoephed.rine closely follows that of
l-ephedrine, d-pseudoephedrine and amphetamine ani the difference appear-s to
be quo.ntitative.
D-eio rpseudoephedrine is excre ted in uri ne of th e rat, rabb it and man
uncbanged, AporoximateIy 40% of th e drug given orally was recovered in
urine of nan unchanged wi.t.h.ln six hours. The drug was detected in urine
omhour- afto l' oral administrat ion and could sti 11 b0 detected in urine
twenty-sevon hour-s later. D-norpseudoephedrine was detected in rat bile and
in milk of lactating rats.
The absence of gross am histopathological Les.ions in suckling young
rats, even though d-norpseudoephedrino was detected in milk, is consistent
with observation in adult rats fed the pure drug wber-e no significant lesions
were found.
The present study shows that d-norpseudoeptedrine is relatively
unimportant in the overall consideration of C-=--a--t-=h.a.a...~ -e--=d..ulis toxicosis. Pntholo- -r •
gical changos observed in rats and rabbits fed Catha material can generally •••• -;;;e •• - •••••••
be attributed ·co the presence of tannins in the IIDterial. In par-tdcu.Lar-,
the changes in the gastrointestinal tract, the Ii ver and the kidney were
simulated by adm:inistration of conmercial tannins intragastrically. The
feeding lnbits of individuals can influence toxicity of tannins considerably
as shown by re sult s of feeding rats with tannic acid incorporated in food and
also Lntz-agast.rd.caLl.y , Even wher-e no lesions were found, 9..§:.th.I9I;I1terial
caused a retardation in the rate of growth possibly by interferring v,ith
absorption 0 f food from the gastrointestinEll tract.
The study suggests tho need for additional research to establish whether
coagulative necrosis observed in some rats and rabbits fed Q.Cltl¥!n.aterd a.L
is a truly toxio effect.
Since tarmins are widespread in the plant Idngdom and in SOIll3conmon
foodstuffs (o.g. tea, sorghum and vegetables) thore appears to be little
tunrrins YiOrOfound to cause somo 10ai.ons , It would be more logicnl to consider
tho question of to.nnins toxity in G wi.dor- can text as hi s boon doro by sonn
workers. Till socio.l-cconomic problems posed by the excessive consuropti on
of Q.c."th.!2:. nrrtcrtinl, are outside tho immediate consideration of this wor-k ard
nccordin[~ly, no attempt is nude to discredit Cc.tho. ~~ ll.'.:terin.l on this ba sd.s , | en |
