Search for New Natural Sources of Morphinans I

HUBERT G. THEUNS, 2 H. LEO THEUNS, 3 AND

ROBERT J. J. CH. LOUSBERG4

Codeine, medically the most widely used opiate, is mostly derived from mor-
phine, isolated from opium and poppy straw (Papaver somniferum, opium poppy).
Morphine, however, is greatly misused by illegal conversion into its diacetyl-deriv-
ative: heroin. The discovery of an efficient alternative medicine or a source for
codeine other than opium poppy may contribute to a curtailment of the heroin
market. No major adverse properties should be present in such a new medicine or
codeine source. In this paper the search for the latter is discussed with regards to
the natural occurrence of morphinan derivatives and the biosynthetic pathways in
available plants. Economic and social problems connected with the introduction
of a new biological source for opiates are reviewed.

In the international fight against heroin--the diacetyl-derivative of natural (-)-

m o r p h i n e - t h e Turkish Government decided in 1971 to prohibit the cultivation
of the opium poppy (Papaversomniferum L.) beginning with the autumn of 1972
(U.N. Document, 1980). Turkey was impelled to take this action by many reports
on the diversion of opium from legal cultivation into the illicit market. At the
time, this gave cause for the fear of a possible shortage of medically useful opiates,
especially codeine.
In the years immediately following the ban on cultivation, the Turkish Gov-
ernment saw itself confronted with rising social resentment, because of the poor
economic conditions of the affected areas and failures in the cultivation of sub-
stitute crops, as a result of poor soil and adverse climatic conditions. The Turkish
economy was sustaining losses because of the suppression of poppy cultivation,
whereas other producers were profiting from a rising demand for opiates for
pharmaceutical purposes and were replacing Turkey as a supplier country (U.N.
Document, 1980).
In 1974, therefore, the Turkish Government lifted the ban on poppy cultivation
in about 7 provinces, but prohibited the incision of poppy capsules and conse-
quently the production of opium from the dried latex exuded from capsules upon
incision. The final aim of this change from opium to poppy straw production was
the establishment of a national alkaloid factory in Turkey, in order to process the
relatively low-value straw into poppy straw concentrate and refined morphine
derivatives. The United Nations encouraged Turkey to bring this factory into
operation as soon as possible and assisted in finding a contractor (Knoll, German
Federal Republic) to build it (U.N. Document, 1980). The investment costs of
the factory were estimated in 1980 at approximately 33 million U.S. dollars (U.N.

Received 26 December 1984; accepted 10 March 1986.

2 Research Scientist, Organic Chemical Laboratory, State University of Utrecht, Utrecht, The Neth-
erlands.
3 Senior Lecturer Development Economics, Department of Economics, Tilburg University, Tilburg,
The Netherlands.
4 Director of Public Health for Drugs, Ministry of Welfare, Health and Culture, Leidschendam, The
Netherlands.

Economic Botany, 40(4), 1986, pp. 485-497

9 1986, by the New York Botanical Garden, Bronx, NY 10458
486 ECONOMIC BOTANY [VOL. 40

Document, 1980). Although at this moment the factory is still far from operating
adequately at or near the planned capacity, the actual outlays amount to about
53 million U.S. dollars. The resulting uncertainty with regard to a continuous
supply of opiates for medical use, combined with a substantially increasing de-
mand for such opiates, made it worthwhile, if not necessary, to give serious
consideration to other sources of opiates (morphinan alkaloids).
Predictions that synthetic drugs would replace the so-called natural narcotic
drugs have not been substantiated. The synthetic narcotic drugs have not gained
a large relative share of the market (U.N. Document, 1980), despite their more
predictable production benefits and their insensitivity to the whims of climate.
Therefore, countries other than the traditional suppliers focussed attention on
new natural sources of morphinan alkaloids as substitutes for the opium poppy.
Among these, plants of the Papaver section Oxytona Bernh. (Macrantha Elk.),
especially Papaver bracteatum Lindl., proved most promising: the latter species
contains almost exclusively the alkaloid thebaine, which can serve as an excellent
substitute for morphine as starting material for chemical conversion into codeine,
medically the most widely used opiate.
Substitution of this particular Papaver species for opium poppy as a source of
morphinan alkaloids may contribute to a curtailment of the heroin market for
the following reason. Heroin is derived from morphine, and the latter compound
is absent from this alternative source of morphinans. The chemical conversion
of thebaine into heroin requires both advanced chemical skill and equipment,
which makes such procedure less likely to be used illicitly (Fig. 1).
The cultivation of Papaver bracteatum for commercial purposes has largely
been frozen on the recommendation of the United Nations Commission on Nar-
cotic Drugs: 1 XXVII 'Restriction of cultivation of poppy,' 835th Meeting, 24
February 1977 (U.N. Document, 1980). Statistics are reported to the International
Narcotics Control Board on the basis of Resolution 2 XXIV of the Commission
on Narcotic Drugs: 'Voluntary Reporting of Statistics of Cultivation of Papaver
bracteatum,' 2-11 February 1971 (U.N. Document, 1980). Some countries, like
Yugoslavia, the United States, Switzerland, and the United Kingdom, seem to
proceed with cultivation.
The recommendation of careful consideration of possible P. bracteatum cul-
tivation for commercial purposes is partly prompted by fear of negative conse-
quences for the economic structure of the traditional suppliers of P. somniferum
raw material, if large-scale cultivation of P. bracteatum should be introduced in
the industrial countries of the Western Hemisphere.
In view of the present overproduction of morphine (estimated by the United
Nations International Narcotics Control Board at 50% for 1982) and the world-
wide increasing amounts of heroin on the illicit market, this policy cannot be
considered to be effective as to the heroin problem. U.N. Resolution 47 l, sup-
porting the restriction to import opiate material only from the traditional sup-
pliers, India and Turkey, may in the end even have adverse effects on the econ-
omies of these countries (see below).
New natural sources of a natural compound are generally not taken into con-
sideration if a reasonable synthetic production of the desired compound is pos-
sible. Despite considerable improvements in the total synthesis of codeine and
similar compounds (e.g., Beyerman et al., 1976; Szfintay et al., 1980; Brossi, 1982),
1986] THEUNS ET AL.: NATURAL MORPHINANS 487

AC~ MeO0
' ~ H NMe \r,/~H~NMe
AcO.L.~ H HO.L~ H
HEROIN CODEINE

2
MeO0
~ HO3 ~ ~ ~
0 'LI'~.,~'~
" I / ~ ~Me ~ ' ~ u ~Me
MeO ~ " ~ HClOL..~8 H ,7
7
THEBAINE MORPHINE
Fig. 1. Structural formulae of heroin, codeine, thebaine, and morphine.

that procedure, however, seems still more complex and expensive than the iso-
lation of morphinans from natural sources.

USES OF MORPHINANS

In addition to uses based on its narcotic properties, the opium poppy and other
Papaver species have found many uses (Duke, 1973). The earliest reports on the
use of poppy in medicine presumably date back to Hippocrates, 460 B.C. (Ba-
zilevskaya, 1928).
Since the isolation of morphine from opium by Sertiirner in 1805, this substance
has been available in a pure form for medical use and pharmacological evaluation.
The high potency of morphine and its high addiction liability limit the use of this
compound, and consequently attention was shifted to the less potent alkaloid
codeine, which is now the most widely used opiate, having a relatively low abuse
potential. In fact, about 90% of the legally produced morphine is converted into
codeine (U.N. Document, 1974) and some other compounds of minor quantitative
importance.
Codeine is used mainly as an antitussive agent, but also as a nonnarcotic an-
algesic. Recently, it has been said to be useful in treating malaria patients. 5 Its
use in the treatment of diarrhoea, however, is out of date, because more effective
substitutes are now available.
For mild to moderate pain, codeine is effective in relatively nontoxic doses,
but for severe pain alternative drugs are preferred because of the side effects of
high doses (Eddy et al., 1968, 1969; WHO-Scientific Group, 1972). Synthetic

5 Communication at February 1982 Vienna meeting of U.N. Commission on Narcotic Drugs.

488 ECONOMIC BOTANY [VOL. 40

alternatives are available that may be equivalent, though none is clearly superior,
to codeine for the relief of mild to moderate pain (ibid.).
For the relief of local irritation of the respiratory tract, alternative drugs are
available with a lower dependency liability and fewer side effects, but none of
them is superior to codeine (ibid.). The use of codeine-substituting agents is stated
to "result in no particular gain and probably no particular loss" (Eddy et al.,
1970). It is often stated, however, that there are no adequate substitutes for
codeine, and that this compound is still needed (U.N. Document, 1974; Cochin,
1975; Greentree, 1978). Indeed, there is no known substitute for which the phar-
macology has been studied as extensively as that of codeine. Moreover, in medical
practice codeine is still the agent of choice against severe cough.
Because of the objective to reduce the production of morphine--a compound
that is highly liable to abuse--a keen interest of researchers in potential alternatives
for codeine is justified.
However, if codeine production were not accompanied by morphine production
there would be no reason to search for a substitute for codeine other than for
economic reasons. Thus, the consideration of alternative morphine-free plant
sources for codeine may eliminate the major disadvantage that accompanies the
production of this compound.
A limited production of morphine, a potent narcotic analgesic, which is very
useful in the treatment of severe pain, may remain necessary. Limited production
of P. somniferum for this purpose will be more easily controllable than today's
large scale production in vast areas, often in rather inaccessible regions that are
difficult to oversee. Morphine, however, may also be prepared in high yield by
O-demethylation of codeine (Rice, 1977), a procedure which is completely unfit
for application within illicit channels and which may totally eliminate the need
for production of P. somniferum for alkaloid yield.

BIOGENESIS OF MORPHINANS

The range ofmorphinans in different plant species depends on the biosynthetic

pathways available to them. The search for a potential replacement of Papaver
somniferum should, therefore, be guided by our present knowledge of the bio-
genesis ofmorphinans. The biosynthetic pathways leading to morphinan alkaloids
are given in Fig. 2 (Bentley, 1971; Miller et al., 1973; Wilson and Coscia, 1975;
Horn et al., 1978; Fairbairn et al., 1978; U.N. Document, 1978; Borkowski et
al., 1978). Within the scope of this paper are included only 3,4-disubstituted
morphinans, which have the same spatial arrangement around C- 13 (S) as natural
(-)-morphine. This stereochemistry is vital for the pharmacological activity.
Little is known with absolute certainty about the earliest stages in morphinan
alkaloid biogenesis. Especially the allocation of methyl ether functions and the
stage of the N-methylation step in the earlier precursors and alkaloidal inter-
mediates are only tentative. It should be noted that biosynthetic proposals usually
are given starting from, or proceeding through, compounds having a specific
location of methyl ethers. This is not always correct, since sometimes the meth-
ylation steps proceed after the completion of the structure (cf. the biosynthesis of
the dibenz[d,f]azonine alkaloid protostephanine, as investigated by Battersby et
al., 1974, 1977). Nevertheless, it is convenient and usual to present biosynthetic
1986] THEUNS ET AL.: NATURAL MORPHINANS 489

,., ,et~l,~

phenethylamne ph~y kI4an~ phenylpyr~ ~

OMe

I
tyromlne tyros4ne p - hyO-oxyPln~ylpyruv~ acid Meo Meo ~

MO ~ HO ~ ,
NN~e NMe N~4e
HO ~ HO COOH Z HO~O 0
Me0 Me Me0
H OH
dopOmlne 3,~-d~ydr oxyph~yloIo~e 3 4~dhydt oxyphenylpyr uv~ ac~
~lu~0rld~ ~lthar~ne~-I

S' thabo,~

pl0
HO0C
NH
OH ~
HO ~N
0H
I

NtAe
)
Ne

Nk~e
......... :).
16-hyffmxy ihebol~
l~0_hydrox
yc~dmno~
H

R
OH OH HDCHzO o l/.fl-hyd~x ycode~ taeO
o r , p o ~ {R: Mel
no?kludonosoi~ c~boxyllc OCKI 1,2~ehydr~k~udrl~hne
I

HO H NH OH rx~'la~carr~~ HO H

o~ OH

1 1
MeO MeO
HO -NMe HO Me
HO H NM ~ OH ~--~ OH

e 0~e ~0Me
ced~ ~ph~ ~ph~e
I-I-te~uhne 1,2-dehy~elcul~m ~ E.I.r ehc=lne

1 1
Codmne N-omd~
1
~ r p h ~ N-oxld~

Fig. 2. Biosynthesis of morphinan alkaloids.

proposals using specifically methylated precursors, and often such schemes are
indeed correct.
The later stages in morphinan alkaloid biogenesis, starting from reticuline, are
better known, due to comparative investigations of alkaloidal precursors with
differing location of methyl ether groups. Precursors and intermediates are mostly
present at enzyme surfaces. Pool sizes of many intermediates are very small.
Consequently, the intermediacy of compounds like salutaridine, salutaridinol-I,
neopinone, and codeinone could be inferred only by means of sophisticated tech-
niques from feeding experiments with radioactive precursors (Barton et al., 1965;
Parker et al., 1972).
In contrast to the fairly accurate knowledge of many biosynthetic tranformations
leading to the morphinan alkaloids, comparatively little is known about the en-
zymes operating in the biosynthetic pathway (Mouranche and Castes, 1978; Hodges
and Rapoport, 1980, 1982a).

N A T U R A L OCCURRENCE OF M O R P H I N A N S

Literature reports on the natural occurrence of morphinan alkaloids are often

rather confusing. In the very early chemical literature the presence of morphine
was reported or alleged for a number of plant species. Later investigators could
not always reproduce such findings. Fulton (1944) gives a compilation of such
data: The plant species, for which the presence of morphine was erroneously
claimed, include Papaver rhoeas (corn poppy, field poppy), P. orientale (oriental
poppy), Eschscholzia californica (California poppy), and Argemone mexicana
(Mexican poppy). Furthermore, Fulton mentions a folk belief that wild lettuce
(Lactuca virosa), and sometimes even ordinary lettuce, contains morphine. The
attribution of morphine in this plant has never received any chemical support.
490 ECONOMIC BOTANY [VOL. 40

Table 1 Natural occurrence of morphlnan alkaloids.

PAPAVERACEAE Alkaloids reported References

Gleuctum flavu~ salutarldlne (0,3%). 5hafiee e t a l . , 1977a.

Glaucium vltelliaum salutaridine (0.2~). Shafiee e t a l . , 1979.
Papaver alblflorum subsp, albifloru~ a theBalne (0.11); thebalne metho-salt (trace). Slavfk et e l . , 1981,
~, aIbiflorum subsp, austromoravic~ thebaine (trace). $1avik e t a l . , 1981.
~. armen~acu~ thebaine (major alkaloid). Philllpson, 1973a.
~. bracteatum thebalne {3.6~); codeine and neoplne (traees)~ Lalezari et a l . j 1974; K~ppers et al.~ 1976;
l~B-hydroxycodeinone and -codeine (traces); Theuns et e l . , 1977;
thebaine N-oxides (traces)~ orlpavine (trace); Phillipson et e l . . 1976; Hodges e t a l . . 1977;
thebalne metho-salt (trace); salutaridine (major RDnseh and Schade~ 1979; Phillipson et el.,
alkalold) b . 1Ogle.
P. c~tlndrfcu~ salutarldine {trace), thebaine (0,051), and Sar~yar, T982,
oripavine (O.O7~).
P. decaisnel ~ r p h i n e {minor a l k a l o i d ) , thebaine, codeine, $1avfk, 1980.
and thebas metho-salt (traces).
P. dubiu~ morphine (dublously). Duke. 1973.
~. u__~
~ c
salutaridlne (0.I~); thebalne (0.15~). Konowalowa e t a I . . 1935; P h i l h p s o n e t a ] . ,
1973b.
~. h)bE~.d~ morphine (dubiously). Duke, Ig73.
P. inter~edium theba[ne (dubiously; Interspecific hybrids), KOhn et 81., 1970.
P. iranicum thebaine (I~ in dried aerial parts), Lalezarl and Shahee. 1978.
P. orlentale oripavlne (Im2~) and thebalne (0.4~); Shafiee e t a l . , 1977b;
saluter;dine (major alkaloid)b; orlpavldine Phillipson et el., 1961a; Israilov et al,~
(minor alkaloid). 1977.
P. oreophllu~ thebaine (conc, unkna~n). Maturov~ e t a l . , 1966.
~. pseudo'orlentale salutaridine (O.12i)j thebaine (major alkaloid); baHyar and P h i l l l p s o n , 1977; Phtlhpson et
oripavine (minor aIkaloid). a l , , 1981a; Coldblatt, 1974.
~. rhoeas morphlne (dubiously); thebaine )trace), McNaughton and Harperj Ig64p and Duke, 1973;
Jusiak e t a l . , 1966.
P. seti~erum morphine and thebalne (major alkaloids), Asahina etal., 1957.
codeine (~inor alka)oid)_
~. ~omniferum morphine (major a l k a l o l d ) , codeine (minor K~hn et al.~ 1970;
alkalold}; neopine (trace); thebaine (major Nyman, 1978a;
alkatoid); salutarid(ne (trace)~ normorphlne Proksa et e l,, 1979; H i l l e r et a1., 1973;
(trace); IO-hydroxycodeine (trace; dubiously); K~hn and Pfelfer, 1963;
16-hydroxythebaine (trace); 6-methylcodeIne Brochmann-Hanssen and Nielsen. 1965;
(trace; dubiously); codeine N-oxide major isomer, Brochmann-Hanssen e t a l . , 1972; K~hn at a l . ,
thebaine N-oxldes, and morphine ~-oxides (traces); I970; P h i l l i p s n n et at., I976j
pseudo~orphine (trace; dubiously); oripavine ~ushinskaya et at.~ 1971~ Nielsen et al.~
(trace). 1983.
P. strl~osum d thebatne (dubiously; interspecific hybrids). K~hn et e l . . 1970.
P, s~riacum theb~ine (trace). Slav~k and S1avikov~. 1976.
P. tauricola thebaine (minor alka}oid); selutaridine {0.25~), Philllpson et el., lg81b; Sarlyar, lgB3a.
~. trinlffoliu~ thebaine end sa]uEaridine {O.OS~ and 0.01~, rasp.]. Sar~y~r, I~3b.
P. urbanlanum salutaridine and O-methylsalutaridlne (cone. Manushakyan e t a l . , lg6g,
unknown).

EUPHORBIACEAE
e

Croton belsamifera salutarldine (cone. unknown). Chambers et e l., 1966.

C. bonplandtanum 3=methoxy-4,6-dlhydroxymorph(nandlen-7-one f (trace), ti.ar, et e l., 1981,
~. discolor 8.14-dihydrosalutaridine (cone. unkn~n). Haynes et e l., 1967.
C. flavens s a l u t a r t d l n o l - [ (cone.unknown). ~antav~. 1970.
~. l i n g e r i e 8~l~-dlhydrosalutaridine and -norsalutarldine Haynes et e l . , 1967.
{cone. unknown).
C. salutarls salutaridine and N-nor~alutar~dine (conc. unknown). Barnes and $oeiro. 1981.

APOCYNACEAE

gau*olfla serpentina thebalne. Hofmann, 195~,

LOGANIACEAE

Str)chnos melinoniana thebaine )dubiously; the plant materia) got B~chli et a1.j 1967.
contaminated wlth opium alkalolds during work-up
in an opium factory).

a Earlier named P. dubi.L~ subs b. alblflorum; b Within the section Ox~tona the ploidy level is to be preferred over other characteristlcs. Therefore, the
p~ant material having a chrc4nos~ number 2n = 28, which was regarded as ~. pseudo-orientale by Ph~lhpson et al.~(1981a)~ must be ranked as P. orlentale,
whereas the plant material having 2n = 14j must be i d e n t i f i e d as P. br~cteatum; c Synonyms: P. caucasicum, P. florlbundum~ d Posslbly a variety of P.
rhoeas~ e The n~rphlnan alkaloids found within this plant family often are acc~panled by their racemlc forms" F The structural assignment of this alkalold
is not certified, because no optlcal rotation data were glven.
1986] THEUNS ET AL.: NATURAL MORPHINANS 491

The alleged presence of morphine in hops (Humulus lupulus) is a special case.

Morphine was never claimed to be isolated from this species, and the alkaloid
"hopeine," which was said to be obtained from hops, was never anything but a
blatant fraud (Fulton, 1944). The material sold at the end of the 19th century
throughout Europe under the name "hopeine" was a mixture of morphine and
cocaine and had nothing at all to do with hops. Nevertheless, 2 Russian reference
books mention morphine (and "chopeine") for hops (Sokolov, 1952; Orekhov,
1955).
A last point to be mentioned in this connection is the confusion sometimes
caused by the indiscriminate use of plant names. P. somniferum varieties from
China or the Far East have been named "Oriental poppies," whereas P. orientale,
P. bracteatum, and P. pseudo-orientale (Goldblatt, 1974) are the only true Oriental
poppies. Further confusion arises from the use of the terms "indigenous poppy,"
"domestic poppy" (usually for P. rhoeas or P. somniferum), and "garden poppy"
(P. somniferum) (Fulton, 1944).
Some data on the natural occurrence of morphinans are given in Table 1. This
table does not further specify the infraspecific variations (chemical varieties) noted
in several species (Phillipson, 1983). It merely summarizes literature data.
In particular the reports on the findings of representatives of this alkaloidal
class within the Euphorbiaceae, Apocynaceae and Loganiaceae (dubiously) deserve
attention from a biochemical point of view. Also interesting is the report of the
production of morphine and thebaine from in vitro tissue culture of P. rhoeas
(Khanna and Sharma, 1977), a species which normally does not yield these al-
kaloids.

I N T R O D U C T I O N OF A NEW NATURAL SOURCE OF MORPHINANS

The codeine equivalency of natural morphinans is dependent upon the avail-

ability and ease of their chemical conversion into codeine. Salutaridine and the
epimeric salutaridinols may be converted into thebaine with 80% overall yield
(Sohar and Schoenewaldt, 1975), whereas the chemical conversion of thebaine
into codeine may be attained in 80-90% overall yield by several procedures
(Theuns and Salemink, 1980). Presently, codeine is prepared by methylation of
morphine (Ikonomovski, 1973).
Promising new natural sources of codeine equivalents include (Table 1) Papaver
fugax, P. iranicum, P. armeniacum, P. albiflorum subsp, albiflorum, P. oreophi-
lum, and P. orientale, though none of these is superior to P. bracteatum, a species
which has a high content of thebaine as the main alkaloid. Because thebaine is a
compound with a good codeine equivalency, the latter species must be considered
the most promising substitute for P. somniferum at hand.
In commercial exploitation of a new plant source of codeine equivalents, many
problems must be faced. Most analytical, agricultural, and chemical problems are
being studied by various research groups (e.g., Seddigh et al., 1982). The factors
governing social acceptability, however, have largely been neglected. This resulted
in political pressure in the countries presently growing P. somniferum to abandon
the P. bracteatum research. U.N. Resolution 471 restricts the export of opiate
raw materials to the traditionally P. somniferum-growing countries.
Because of the unlikeliness of permanent political suppression of the cultivation
492 ECONOMIC BOTANY [VOL. 40

of safer opiate-yielding species in countries not yet growing natural morphinan

sources, one should consider the macro- and micro-economic as well as social
implications for the traditionally P. somniferum-growing countries. Crop substi-
tution programs should be directed towards economic feasibility and local social
acceptability in the countries in question. No doubt, such will be a complex
process, which will take many years. The Turkish attempt to suppress the culti-
vation of P. somniferum at once was doomed to failure (Cochin, 1975).
Promotion of P. bracteatum research in the traditionally P. somniferum-grow-
ing countries may contribute to the economic survival of the local farmers, pro-
vided the climatic conditions of the traditional growing areas are favourable for
P. bracteatum cultivation. There is a good prospect for this in Turkey, but not
for India. In the latter country the narcotics farms probably have to be translocated
to other areas having a more suitable climate. Moreover, India differs from Turkey
in having mainly opium production, which is very labour intensive (Krikorian
and Ledbetter, 1975). Enormous structural consequences for the economic life
and habits of the farmers will result from suppression of its production. Probably,
harvest of"bractium" (the dried latex ofP. bracteaturn) would be needed in order
to maintain employment. The known instability of thebaine, when in solution or
exposed to light and air, may prevent, however, a remunerative production of
"bractium."
If no international agreement with respect to these problems is reached, the
countries in question may end up with vast economic problems, when the nar-
cotics-consuming nations decide to promote codeine self-sufficiency, be it for
political reasons, or in order to cut down on the heroin problem (Theuns, 1981).
In any case, a quota system should be established, in order to avoid overproduc-
tion. Furthermore, it is questionable whether the traditionally P. somniferum-
producing nations will appreciate being patronized (Anonymous, 1980) and being
dependent for the sale and price of their agricultural product on buyer countries,
which at any moment may decide to rely on opiate self-sufficiency by taking P.
bracteatum "off the shell" (Anonymous, 1980).

ALTERNATIVE SOLUTIONS

A marginal contribution to a decrease of the heroin problem may be expected

from the present United Nations policy to increase the narcotics production per
unit area of cultivation. The selection of P. somniferum varieties with low mor-
phine content and a high thebaine (or codeine) content is a recent development
(Nyman, 1978a,b, 1979), which might be considered promising with respect to
reducing the heroin supply. However, a relapse of the yield of morphine is not
unlikely, and such may easily be promoted by the criminal insertion of seeds of
morphine-yielding varieties. The substitution of such selected P. somniferum
varieties must, therefore, be judged as a quite unrealistic approach to the heroin
problem, although for biosynthetic studies it is highly interesting. Relapse to
morphine-yielding plants is even more likely in interspecific hybrids, such as P.
somniferum x P. bracteatum.
A topic to be mentioned is the discovery of natural (animal) peptides having
a morphine-like action (Hughes et al., 1975). In view of the fact that these en-
dorphines have the same addiction liability as morphine (Wei and Loh, 1976;
1986] THEUNS ET AL.: NATURAL MORPHINANS 493

Van Ree et al., 1978; Chau-Pam, 1978) and that their metabolites seem to exhibit
profound pharmacological actions (De Wied et al., 1978; Verhoeven et al., 1978),
their medical use as substitutes for morphine and codeine will be limited, for the
present.
The production of opium alkaloids by in vitro tissue culture ofP. somniferurn
(Anonymous, 1982) is a promising development, which may help to prevent
leaking of opiates into illicit channels (Hsu, 1981; Hodges and Rapoport, 1982b;
Kamo et al., 1982; Staba et al., 1982; Zito and Staba, 1982; Heinstein, 1985).
For the present, however, yields obtained are too low for commercial exploitation.

ADDICTION LIABILITY OF THEBAINE AND OTHER

PAPA VER BRACTEATUM ALKALOIDS

The addiction liability of thebaine, its derivatives, and of the minor alkaloids,
reported for Papaver bracteatum, has been studied. No case of thebaine abuse or
of illicit production of its derivatives has been reported (WHO-Advisory Group,
1980). Should heroin cease to be available, such abuse is not considered likely
either (U.N. Document, 1976). The minor alkaloids of P. bracteatum occur in
minute amounts only and can far easier be isolated from other plant species
(Kettenes-Van den Bosch et al., 1979, 1981). Thus, the abuse potential of P.
bracteatum alkaloids may be considered neglectable (WHO-Advisory Group,
1980). In this respect there is no reason to fear that production of thebaine from
P. bracteatum "'might let some unanticipated genie out of the bottle" (Anonymous,
1975).

ACKNOWLEDGMENTS

This paper results from research carried out by the first author as a Consultant to the United Nations
Division of Narcotic Drugs. The authors are indebted to Dr. S. D. Cook for linguistic corrections of
the revised version of the manuscript.

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Book Review
The Illustrated Plants of Special Uses in Taiwan. Feng-Chi Ho. Taiwan Museum, Taipei
City, Taiwan, R.O.C. 100. 1985. 219 pp. N.T./$600.00, US$15.00 (+ postage).
This elegantly illustrated book will fascinate any economic botanist. It consists mainly
o f six sections according to use: 1) Fragrances; 2) Insecticides and insect-repellents; 3)
Industrial oils; 4) Dyes and inks; 5) Fibers; 6) Cooling and medicinal beverages, jelly, and
soup. There are 209 species shown in full color; some only a branch-tip in flower or fruit,
others, an herbaceous plant or bush in bloom, or a portion of a tree or palm, accompanied
by separate close-ups o f flowers and/or fruits, seeds, and, occasionally, extracted fiber.
Introducing each section is a headlined page reproducing one of the illustrations within
the section.
Each subject is clearly identified by family and botanical binomial. The brief explanatory
text is entirely in Chinese but the pictures are eloquent. Included are many plants of broad
interest: tuberose, frangipani, crape jasmine, honeysuckle, basil, cinnamon, sweetpea, or-
chid trees, magnolia, lotus, Grand Duke jasmine, roses, grapefruit, lemon, ' H a n d of Buddha'
citron, orange jasmine, sandalwood, fennel, ginger-lily, pyrethrum, camphor, tree-of-heav-
en, tung nut, candlenut, physic nut, castorbean, peanut, African oil palm, sesame, mango,
annatto, tallowwood tree, logwood, indigo, betelnut, pomegranate, sisal, ricepaper plant,
kapok tree, Panama-hat plant, papyrus, flax, cotton, kenaf, paper mulberry, coconut, jute,
ramie, sweet-herb-of-Paraguay, Job's-tears, rosary pea (seeds poisonous; dried leaves and
stems used for "tea"), munghean, aloe, okra, roselle, passionfruit, plantain, coffee, and
cacao. Though these names do not appear in English in the book, finding is facilitated by
a detailed Table of Contents providing family and species names in the order of their
apperance, and an alphabetical Index o f scientific names. There is also a 10-item Bibli-
ography in Chinese and a Chinese subject index. Dr. Samuel Lee, Associate Dean, College
of Engineering, University of Miami, who revealed the plan of the book to me, pointed
out that the leaf decoction of var. awkeotsang of the c o m m o n creeping fig (p. 199) is a
remedy for appendicitis and bladder infection; the decoction o f Euphorbia thymifolia (p.
183) is drunk cold or applied on rashes; the aggressive cogon grass (p. 185), a bane o f the
tropics, is boiled to make a medicinal "tea." He spoke enthusiastically about the jelly made
from Mesona procumbens (p. 190) as a summertime refreshment (possibly much like our
familiar mint jelly). In fact, he was delighted to scan the book and it is quite likely that it
will be warmly greeted by Oriental residents in all walks of life in this country, in addition
to plant-minded scholars. I might add that Aloe vera (L.) Webb. (p. 195) is a synonym o f
the preferred Aloe barbadensis Mill., the much-exploited form of which has yellow flowers.
JULIA F. MORTON, UNIVERSITYOF MIAMI, CORAL GAaLES, FL 33124