I UNITED NATIONS

W O R L D I - I E A L T N O R G A N I Z A T I O N

NATIONS UNlES

WH O/X F'D/9 1 0 February 1949

OR I G INAL : ENGLISH

EXPERT COWIITTEE ON HAB IT-FORNING DRUGS

L./ Report on the first session

Held 24-29 January 1949, Pala is des Nations, Geneva.

Members: D r . J. BOUQUET, Ex-Inspecteur des Pharmacies, Tunis

D r . N. B. EDDY, Pr incipal Pharmacologist , National I n s t i t u t

United S t a t e s Public Health Service,

Washington (chairman)

D r . J .R. NICHOLLS , Deputy Government Chemist,

Goverment Lab oratory, London

Dr . P.O. '#OLFF, Buenos Aires

Absent:Dr. H.P. CHU, Professor of Pharmacology,

National College of Medicine,

Shanghai

Secretary: Dr . R. MUTIER, Assistant Director-General

Observers: ilnr. V. PASTUHOV, Chief of Section, Division on

iVarcotics, United Nations

M r . A.E. FELKIN, Secretary, Permanent Central

Opium Board and Drug Supervisory Body,

United Nations.

m. L.F. ATZENIIILER, ~ s s i s t a n t - s e c r e t a r y ,

Permanent Central Opium Board and

Drug Supervisory Body; United Nations

Professor H. FISCHER ( ~ u r i c h ) , attended pa r t of t h e

session (25-26 ~ a n u a r y ) i n h i s capaci ty of member 01. the Permanent

Central Opium Board and of the Erug ~ u ~ e r v i s o & Body.

The agends having been adopted, D r . Eddy was e lected

Chairman and D r . 1fJolff Rapportwr .

The question whether, the preparati0.n .Valbinel was t o be exempted

from the provisions of the 1925 Convention was discussed, specia l

s t r e s s being l a i d on t h e content of dihydrooxycodeinone hydrochloride,

t he pos s ib i l i t y of recovering t h i s alknLoid from the preparation, t he

presence of p h e n y l e t h y ~ r n ~ o ~ l ~ e a and whether t h e n u @ s of t a b l e t s

contained i n a tube was such tha t , taken shd t aneous ly : by,.bn addict,

they k d maintain h i s s t a t e of addiction. ,

The following resolut ion was passed: , .

The Committee, . flaving considered a request from the French Goqernment t o have t he preparationvValbine exempted from the provisions of t h e .l925 Convention by appl icat ion of i t s Ar t ic le 8,

Is of' the opinion' that &eh exemption should not be granted in favour of VaZbine# ,and

RECWNDS that , t h i s decision be no t i f i ed t o the Economic and Social, council of t he United Nations f o r transmission t o thd French Government.

2. Notifications by t h e governments of t h e United S t a t e s of America and of t h e United Kingdom concerning METOPON (Doe6 .'iVHO/HFD/2 and %HO/HFD/8) . W

The Committee considered t h e no t i f i ca t ions from the gdvernments

of t h e Unitec! ~ t a t e s ' o f America and of the United Kingdom a s t o t h e

habit-forming proper t ies of methyldihydromorphinone ide

(Metopon HCl) . On the ba s i s of the observations made i n both t h e mentioned

countries, t he Committee adopted t he following resolution: J . - The Committee,

Having considered no t i f i ca t ions from the Governments of the United S t a t e s of America and of the United Kingdom i n regard t o methyldihydr omorphinone hy2rochlor ide (Metopon HC1) under Ar t ic le 11 of the 1931 Convention,

. , a .

Composition of Valbine? .

~ihydrooxycodeinane hydrchloride 1 mg Phenylethylmalonylurea 3 CP Extractum pisci4iae 2 Cg Extractum pruni Virginianae' 3 C&' Extracturn Crataegi 5 % ,

per, t ab l e t .

Is of t h e opinion t h a t nLthjridihyc!rc noq7hinone and i t s s a l t s a r e habit-f orming drucs , anc!

RECOW~NDS t h a t t h i s op in ion be n o t i f i e d t o t h e Secret:sry-General of t h e United Nations under t h e provis ions of A r t i c l e 11, paragraphs 3 and 5 of t h e 1931 Convent ion,

N o t i f i c a t i o n rece ived from t h c Belgian Government re[;czr6ing 3 . -------.__ - . - - . - - - - -_-----.- ...-a-- 1

acetyldihydrocode ine hydroch lo r idc"G~~e _ _ l _ _ l name : -I hcetyicodone --.I-,-. -- I_C--- ) Tdz6; - E u / I ~ P D / ~ )

The Comi:"ue has consicered a n o t i f i c c t i o n received from t h e

i3olgian Gove:?nment ;vi-tJl r.: s ~ e c t t o acety',6*ihydrocc?deine

(C-, -.3 H 22 0 2 i\i (o,c~,,,cF!,) I - I C ~ + M 2 o;, .

The Committee has no u p e c i f i c information on t h e habit,.foraing

proper ty of ace2,yldihy(frococfeine, but i s of t h e opinion that, t h i s

substance i s conve r t ib l e t o dihydrocodeine which, i? t u r n , i s

convex% Yule t o dihjdromorphine , a h a b i t -f o1:nin;i drug, The s ta tene l l t

wi th r e spec t t o conversion Lo a hczbit..forrning drug a p p l i e s e q ~ ~ a l l y

t o o the r s s f e r s of c?.ihydrocodeine anc? t h e i r s a l t s , %c! a l s o t o

d i l ~ y d r ocodeine and i t s s a l t s ,,

The Committee

RF:COIvBdENDS t h a t t h e Committeeis opinion t h a t Cih)-drocodeine, i t s e s t e r s and t h e i r s a l t s a r e conve r t jb l a t o dihydromorphine , a habit-f orming drug, should be c~mr~iunicated t o t h e Secretary--Generni of t h e United NaSi.ons.

4. Protocol s igned i n P a r i s on 19 November 1948 W..---. __ .-..-.---_ -.v

The Committee no5cd t h a t t h i s Protocol , a l though not h ~ j i.ng

y e t rece ived the necessary number of f i n a l s igna tu re s , i s expec t s? t o

e n t e r i n t o force i n t h e ve ry nerw fu tu re . Therefore, f o r p r a c t i c a l

pwposes, t h e Cclr~mi.~tee ddcided t o proceed a s i f t . h i n Pra t ,oco i were

a c t u a l l y i n fo rce ,

5, 1 -7 ethyl-4--p'henyl.i~ fperidine-.4-.carboyylic as i d ethyl ~ s t e r -" -_-_-_ "" ___ __- _ _.-. "- _"__-__ _____" --..._ "....~.^-..--"".n~U /..-A-

( t he hydronhloridc of which i s known under t h e nrunes of. Dolant in, Demerol, Pe th id ine , PirS.dosa1, e t c , )

The Commitfee tms informed of t h e s t e p s taken i n May 1945 by the

Prcsiden5 of t h e Cou-ncil of t h c League of TJations t o have 7.-~ct,h;~: ?-.

phewl-13iperidine--4-carbowlic a c i d e t h y l e s t e r subjectcr? t o t h e

measures of c o n t r o l provided i n t h c 1925 Con.crention,

~ ~ H o / H E ' D / ~ page 4

The Committee considered, however, t h a t t h e supervision thus

exerc ised i s not s u f f i c i e n t t o ensure t h e i n t e r n a t i o n a l cont ro l of

such a powerful habit-forming drug. Therefore,

Thc Cornnittee i s of t h e opinion t h a t , by v i r t u e of

A r t i c l e 1, paragrn2h 2, of t h e Protocol of 1948,

l-methyl-4-phenyl--piperic!ine-4--carboxylic a c i d e t h y l e s t e r and

i t s s a l t s should be considered as capable of producing add ic t ion

and should the re fo re f a l l under a r t i c l e 1, paragraph 2, Group I

of the 1931 Convention, an8

F,ECO?&V!ENL7S thaz t h i s opinion be n o t i f i e d t o t h e Secretary-.

General of the United Nations.

6 , Other Substances o f the Dolantin type .---v -

Afte r having exgrcssec! i ts opinion on l-methyl-4-phenyl-

piperidine-4-carboxylic acid e t h y l e s t e r ( i tem 5 ) ) t he Committee

bel ieved t h a t the onus was u2on it t o cons ider a l s o t h e manjr o ther

s l~bs tqnces ~f s i m i l a r s t r u c t ~ ~ r e Itnorvn at present , and t,o r n i ~ i c k rcTerence

i s made i n memoranda by Prof. F ischer (doc. E / O B / ~ Rev.1) and

D r . ltrolf f ( doc . ~ H o / K F D / ~ )

From t h e e v i d e v r , before it,

The Committee i's of t h e ailinion t h a t

l - m e t ~ l - 4 - m e t a h y ~ r o x y p h e ~ 1 - i ~ i p e r i i n e - 4 - c r b o l i c ac id e t h y l e s t e r (Bemidone)

l-methyl-4-metahydroxypbenyl-4-propionyleridine ( et o- emi id one )

- 1 , 3 - ~ i m e t h y l - 4 - p h e n y 1 4 - p r o p i o n o ~ - p i i n e (NU-1196)

P -1,3-dimethy1-4-phenyl4-propi~noxypiperidine (NU-1779)

a r e a l l substances of s i m i l a r chemical s t r u c t u r e (type: ~ o l a n t i n ) 2 7 - an.! d ~ f i r l i t c l y haki'; f i , - mii~g, 112 s~;;xLL LL L L . ~ i.,~' i . ; l i # A $-, i) i ' i &L

a c t i o n when t h e Protocol of 19 November 1948 comes i n h fo rce , and

RECOMMENDS t h a t t h i s opinion be notif iec! t o the Secretary-

General of the United Nations,

--v.- -- - <-

- See finnex l.

7. 6-dimethylamino-4,4-diphenyl-3-heptanone and substances of similar type

From t h e evidence before it,

The Committee is of the opinion t h a t the following syrithetic

6-dimethylarnino-4,4-diphenfl-3-heptanone (~aethad one, kmfcione , e t c . )

64imethylamino-5 -rnethy14,4-diphenyl-3-hexanone ( isornethadone )

6dimethylamino-4 ,4-eiphenyl-3-heptanol

6-m~rphol in0-4,4-dii>henyl-3-heptan0n~ ( C, B .l1 1 should de f in i t e ly be considered as habit-forming,3 and should be

noted f o r appropriate act ion when t he ,Protoco'l of 19 Moverhber 1948

comes i n t o force, and

RECOMMENDS t h a t t h i s opinion be no t i f i ed t o t he secretary-

General of the United Nations,

8. Precaut ioxxiry measures with regard t o ' synthet ic substances

The Committee is of the opinion t h a t other compounds of a

s teucture similar t o those re fe r red t o under item 6 (Dolantfn type)

and item 7 (Methadone type) must be under suspicion a s t o t h e i r

having habit-forming proper t ies u n t i l t h e contrary be proved. The

Committee considers t h a t governments shou3.d watch these compounds

with extreme care and should t ake appropriate act ion immediately on

t he discovery of t he addicting proper t ies of any one of them.

With reference t o t h e experience already gained. with some members

of the Dolantin and Methadone groups, i

The Committee

REC-NDS tha t provision should be made i n any new convention,

whereby substances of a par t i cu la r chemical type, analogues of

which have been proved t o be habit-forming, could be placed under l

cont ro l u n t i l such time a s they are shown not t o be habit-forming.

9. Diacetylmorphine

The Committee, having noted the views expressed by t h e Permanent

Ce Board and the Drug Supe B&y on the question of

3 see ~ n n o x ?,

diacetylmorphine, consic?ered t h e inc rczse i n t h e f i g u r e s of constlmp-

t i o n of t h i s substance i n some uf t h e coun t r i e s mentioned i n

document E/oB/~. Reference w a s a l s o made t o Recommendation V1 of

t h e 1931 Convention which was basec! on t h e view ergressec! by t h e

Committee o f Exper t s of t h e Conference f o r t h e L imi t a t ion of t h e

manufacture of nzrcot i c dru;;s (1931), and which emphasized "the h ighly

dangerous cha rac t e r of d iace t j lmorphine a s a drug of add ic t ion and t h e

g ~ s s i b i l i t y i n most, i f no t a l l , c a scs , of r ep l ac ing it by o the r dru,;s

of a l e s s eangerous charac te rq ,

Having hearc! a s ta tement by Professor ~ i s c h c r ~ with which it

f u l l y agreed, t h e Committee expressec? a f e e l i n g of a larm over t h e

e x i s t i n g s i t u a t i o n ~ i t h regar? t o diacetylmorphine and s t r e s s e d t h e

fact t h a t t h e r e a r e 24 c o u n t r i e s i n which diacetylmorphine is no t used

a t a l l . 5

The Committee is of t h e opinion t h a t f u r t h e r information is urgent-

l y needec? as t o t h e rezsons governing t h e present use of diacetylmorphine

i n some coun t r i e s , p a r t i c u l a r l y wi th reg,arc! t o it S p o s s i b l e dispensa-

b i l i t y . Such d a t a might be secure2 through t h e good o f f i c e s of t h e

Yiorld Medical Associat ion, I n add i t i on , d i r e c t i n q u i r i e s might be

undertaken by t h e senc?.ing of an e x p e r t t o c o u n t r i e s where t h e consumption

of diacetylmorphine i s high, i n o rde r t o a s c e r t a i n from l o c a l phys ic ians

anc? h o s p i t a l and s i ckness insurance s e r v i c e s t h e reasons f o r t h e

p re sc r ib ing of t h i s drug,

The Fxpert Committee

EIECOm&NI)S t h a t s t e p s should be taken t o secure information on

t h e use o r d i s p t n s a b i l i t y of c ' izcetylmoq~hinc i n t he va r ious

c s u n t r i e s through t h e dorld ldedical Assoc ia t ion and by sending m

exL2ert t o coun t r i e s where t h e consumption of diacetylmorphine i s

hi&.

See Annex 2

5 h u s t r i a Bulgar ia Greece Lwcemburg Polanc! Spain

United S t a t e s of iimerica

Costa. Rica Cuba Dominican Ke;?ublic Guat ernala Honcluras Nexico Nicaragua Salvador

B r a z i l Chile Colombia Peru . Venezuela

China Japan

EVIDENCE ON THE 2DDICTION POTE??:',',I".LITY OF COiJlPOUllTDS OF THE D O L M I I t "UlD !:BTH!DOPF; TY FdS

( ~ 2 t c by D r . N.B. Eddy)

The Reszaxch Dcpartnent ;f the US Public Haalth Service Hospital

a&xington, Ky., USA, hss carried ?ut t e s t s on the addiction

po t en t i a l i t y X' new synthetic substances of the Dei.~erol and Methadone

types (J. h e r . med. ASS., 2.35, &88-894, 194'7; Proc. N.Y. Acad. Sci.,

51, 1-74, 1948) including the following, as y e t unpublished:

1 l-methyl-4-metahydro~heny~-piperidine-4-carbo~lic acxd

e thy l e s t e r emid id one).

This substance i s p rac t i c a l l y i den t i ca l with Demerol i n the reac-

t i ~ n s which it produces and i n the dosage required t o praduce euphoria

i n post-addicts or t o supp-ess abstinence phenemena of an established

mclrphine addiction. Its addiction poten+,ial i ty then is considered

t o be very l i k e t h a t o f Demerol i t s e l f .

2 l-me thyl-4-me t a h y d r ~ w p h ~ n y l - 4 - p r o p i o n y l - p r d n et o-

Bemidone ) . I n s ingle dose, t h i s substance pr~duce:. intense euphoria i n

former morphine addicts , It read i ly suppresses abstinence phenomena

of an established morphine addiction. The behaviour of men experi-

mentally addicted t o Keto-Bemidone i s very simi1a~- +o the behaviour

of men addictad t o morphine. Tolerance develcped ts sedative action,

the e f f ec t on the e lec t rcencepha lo~am, the erne%ic e f f e c t and the

ef f ec t on the thermal rad ia t ion pain th re shald . Follonring abrupt

withdrawal of Keto-Bemidone af ter ada in i s t r a t i sn f o r 42 t o 60 days,

an abstinence syndrome developed very rapidly ( i n l e s s than 10 hours)

which was so int;ense as t o be regarded as po ten t ia l ly dangerous GO

l i f e , and which declined rapidly.

The evidence i s unequivoc a1 %h : iL lie t =--Bemidone produce S a type

of a d d i c t i m which i s very s i m i l = t o addiction t o the drugs of the

mmphine s e r i e s and which i s S. g rec t t h a t the drug s h ~ u l d n? t be

used i i i c l i n i ca l medi,-ine unless i t can be shmn t o pnssess great

advantage wer the pqtent e ~ a l g a s i c s already available.

This evidence has bean plhescntcd t . the C~mmi.;ei?ner ?f Narc 2tiC.s

o f the United S t a t e s ?f ilmi?rica m d t o the manuf3ccturers wh? h91d the

'V\HO/APD/~ page 10

p a t e n t ln K e t il -2e;r,i4- nc . r~ie l a t t e r ha~~re as a r e s u l t v , , l u n t a r i l y

suspend,d pr:ducti:ri ~f 1<3 t S-Bemid-.ne and p l ans f r i t s rnmkcting.

3 and 4 ;-l ,3-.ciixie t~l-4-pher1yl-4-p.r~pi~:r1 >xy-.pipe r i d i n e and

p -1, j--dimc thyl--4.-pht iyl-?-p i p i . n jxy-piperidin? ( CU-l196 u?d NU-1779 )

Both :-?f th,,se s u b s t ~ i ~ c e s ar? m-)rc e f f e c t i v s t han DemerQ i n the

prqduct i -n -f auph ) r * l a i n p >st-r iddicts and i n t he s u p p e s s i o n c f 8.b-

s t i nencc .;lf sri ? ~ t ~ i , ? ~ i S'., ,d :!,irphini, r ~ d d i c t i - ) n o The $--is-mer i s twice

as. ef fec t iv ; , t ~ c ;lfi-i S j~c>r thrc, r f u r t i ~ n l s 2s effzct j -vu es Dc.rnar~l

' i n t h e s s r t s p o c t s . %:fk, then: ;ri: c.asldered t lir?.~.~e groc tor a d d i c t i ~ n

p:tcnti?Lity th2n ljumer ..L.

5 6-d1mcthyl~iriin~-il, 4-diph3nyl-3-haptpncjl.

This s u b s t m c e !>:L; n t p r ? d u c ~ d i ;uph<xia i n p x t - a d d j - c t s i n t b s

dcszs ~ d - i l i n i s t e ~ c l /9~-120 mg.), and has only very s l i g h t e f f e c t

t hc abstinen-lc 2henmena " m s s t z b l i shed mcirphinc a d d i c t i m . It

?ls> has v3ry wec?k :PC! act,i:n. I t s add ic t inn p ~ t c n t i a l i t y

appczrs t:~ ba lw.

I n t h i s substirnce 2.1 hydrsxyl g 3 u p has bean aca ty la tdd as i n t h e

change frr-,m mxph ine t o her. , in. I n csnsequznce a n d g c s i c a c t i ~ n hes

bzen incr$esed a t l eas t 2s ~LLI::I ;is i n idethadene. The c~mpcund pr;-

duces mnrkcd e ~ i i h x i e i n pmt-addic Ls and re?.dil;y suppresses thd

abst inence phan~mena ,P cn e s t ~ b l i s h c d idd diction. IL i s c ~ n s i d e r e d

,-I I 6-ni:r;~!~~lin:-4,1.-d~.pl~~n.lrl-3-ho~~~n~ne (CB-XI;.

Smzil d2scs (i5-20 mg. ) p r . 3 d - x ~ an i n t e n s e bwt n , t l c n g l a s s i n g

e u p h x i c rd?.cti, n i n p o s t - x l d i c t s ; l ~ x g a r d2ses ceuse a sevcrc t -xic

circul~.t-..1-;. r zc?c l i fn . SwAl d .szs rncrk~dly reduc; t h c in tc?ns i ty r f

abstinunc;, pncn;me,.:,a )f m-.r.phind add ic t s , but " ,~sz pl-ien~i-rc?na r e t u r n

t c t h e i r f nn;r iriti,r,ei ty i n 2 h ~ u r s . This c;rnp>und i s con:,idtrcd

t o h w e a s t rong ~ ic l2 i c t i . n ?s t~nt ic? ; l i t ; r , as grca:, , p r j b d ~ l y , as t h a t

ANNEX I1

DUaTYLMORPHm

(Heroin)

Memoranc?un by Professor H, Fischor

,The danger constituted by heroin is nowadays undisputed*

Widespread heroin addiction i n New York between 1912 and 1920, and the

perilous years between l 9 M and. 1930 i n Egypt ( ~ u s a e l l Pacha) are cases

i n point, Because of few or inadequate control mea$ures, heroin pro-

duction flourished, and i l l i c i t trade i n t h i s product was exploited t o

a remarkable degree of efficiency by contraband dealers, even aPter the

entry into force of the Conventions of 1925 and 19 om tha t time

onwards, the unlawrul production of'herofn grewb and bounds i n

China, par t ly with the help of European chemists. Ever increasing

imports of acet ic anhydride were a clear ineication of the proportions

a~stuned i n tha t country by heroin product ion, which amounted t o dozens

of tons per year.

The heroin smoking-habit introduced in China was a part icular ly

pernicious form of heroin addiction ( nd, e t c, ) . During t h i s

period, the production of diacteylmorphine osci l la ted between 10, 20 and

X tons per year, It i s a known fac t t the time of the Japanese

invasion (1933 t o 1935)$ Japan made g

and Jehol with narcotics, including not only opiwn f o r smoking purposes,

but a lso heroin. During the second. world war, Japan used heroin as a

weapon in carrying out i t s genocidal policy 5x1 Ihnchukuo, You w i l l no , doubt r e c d l the Mulcd.cn factory, whose production of diacety'lmorphine

reached 50 tons annually.

1% would seem logica l t o completely ban the use of a poisonous drug

which has wreaked such havoc throughout the world during the l a s t 50

years. The Convention of 1931 was designed for t h i s purpose, but only

a few countries adhered t o i t s s t ipulat ions, In t h i s regard the Unitec?

States has scrupulously carried out i ts obligations for the past 20 years,

From a medical point of view, heroin shoulc? continue t o be used only if

i t s t a l u e a s a drug can be proved; t h a t is, if no other drup c m fulfil

the same purposes, and it should at l e a s t haGe def in i te therapeutic

q ~ m l i t i e s . In my opinion, none cf t h e aforeraent ioned condi t ions

i s f u l f i l l e d by t h i s d r u ~ .

US e mnttcr of f a c t , he ro in i s g s n e r a l l y cunsiclered a s an

extremely c'angerous dru, . J14ost dgc t o r s an6 h o s p i t a l s r e f r a i n f r o n

us ing it, and ~vould no 9 u b t agree t o i t s c9~mnplete e l imina t ion

tkrout t lout t he I V ~ L 12. I n ;,,ite 9f t h i z , we f i n ? n ~ y r ~ ~ . l v e ? t,nd-7y ill

t h e ilresence of n s i t u a t i a n which i s both anomalous and d i squ ie t ing ,

I n c e r t a i n ccun t r i eg , d o c t ~ r s a r e ; r e s c r i l ~ i n g hcro in vvith ever

i n c r e a s in;, frcqucncjr, a n d i n FiriLani! i n p a r t i c u l a r , t h e r e is cause

f o r alarm.

For doc tors , t h e increased use of he ro in i n v a r i o u s coun t r i e s i s

d i f f i c ~ , l t t o understand, a s t h e o;rini?n of t h e medical body throughout

t h e world is unanimous a s t o t h e harmful na tu re of hero in , both from

e medical and n a r c o t i c viewpoint.

A s

General ly speaking, d iacoty lnorphine i s more t o x i c t han morphine,

a s t h e resul . tant ana lges i c e f f e c t i s from f o u r t o e i g h t t k n u s t ~ o r e

powerful. Its seda t ive and ;7ara ly t ic e f f e c t on t h e r e s p i r a t o r y - system

i s much g r c a t e r t han t h a t produced by morphine, as 0,007 grams of

diacetylmorphine i s s u f f i c i e n t t o b r i n g on r e s p i r a t o r y p a r a l y s i s ,

Diacetylmorphine i s p re sc r ibed f o r t h e same s p e c i f i c i;urposes as

morphine: f o r p a i n f u l cp ,ndi t ims , i nc lud ing thosc caus iq ; insomnia and,

above a l l , f o r i r r i t a t i o n s af t h e r e s p i r a t o r y t r a c t , more ? a r t , i c ~ x l a r l y

t hosc c n c ~ > u n t e r e l i n ,~ulrnonary t u b e r c u l o s i s an,! i n c a s e s of t u b e r c u l o s i s

of t h e la rynx , Diacetylm3rphine i s c ~ n t r a - i n e i c n t e d when dealin; wi th

emphysema, asthma and h e a r t t roub le .

The e l imina t ion of hero in i s c ' i r e c t l y r e l a t e d t o t h e prcscr i ;? t ions

made by doc tors . Heroin can bc prescr ibe? f c r cough cond i t i cns and

i r r i t a t i s n s ir, t h e res ; ) i r2 t cjry t r a c t , as f o r examplc , i n p u l m ~ n a r y

t u b e r c u l o s i s and i n ca ses of t u b e r c u l o s i s of t h e larynx, b u t t o a l e s s e r

degree as a c e n t r a l ana lges i c , In o the r words, t h e s 2 s c i f i c medical

u ses of ?.iacetxlrndrphine a r e not t o be d i s t i ngu i shed from those of o t h e r . . ana lges i c s used i n cau?,h conclitions, such a s mor2hine, a c e ~ , ~ c J L , ~ , G U ~ U L ~ L ~

di lnudide , pernonide, and dicoc?ide,

A s a ct3uch remedy, t h e r e is consequently no medical j u s t i f i c a t i o n

f o r *>refer r ing diacetylmorghine t o o t h e r dru; s , or of even p lac iqg it i n

wo/m/9 page 13

the same category, Possible r epe r~us s ions on the resp i ra to ry t r a c t

and the ease and rap id i ty with which addiction can be acquired, a r e

f ac to r s which c l ea r ly indicate t h a t it cannot be considered as useful

a s t h e above-xpentioned drugs,

A s is indicated i n t h e repor t submitted by the Permanent 0entra.l

Opium Board t o the Social and Zonomic Council on the work a c ~ ~ ~ l ~ ~ i i s h e d

by the Board i n 1948, there are f i v e countries whose consumption of

ylmorphine reached 2 kg, per mil l ion inhabi tants and f i v e a ther

i e s where over 5 kg . xere consumed. By order of highest con-

sqt ion, %hese countries a r e : Italy, New Zealand, Sweden, Austral ia,

and CanaCla, One country inland) uses more than 25 kg . of diacetyl -

morphine per mil l ion inhabitants, In contrast , among t h e 74 countr ies

and 96 colonies and t e r r i t o r i e s mentioned, n t r i e s and 21 terri-

t o r i e s have not made provision f o r d iace t

The following are some of the countr tylmorphine :

United States, Japan, Austria, Bulgaria, Hungary, Spain, Poland, Mexico,

Braz i l and Eg;~pt,

I h e a r t i l y commend tb WHO Expert Cornittee on Habit Forming Drugs

f o r having included i n i ts present programme of work the question of

diacetylmorphine, which i s a matter of serious concern t o the Permanent

Opium Board a s well as t he Drug Supervisory Body, Neither the

n t Central 9 i u m Board nor the Supervisory Body sees the necess i ty

or even the u t i l i t y of increasing the consumption of heroin i n Finland,

I t a l y and other countries, f o r reasons which have been put forward by

cJoctors i n those countries. Lf, i n Finland, sickness insurance

organizations encourage t he use of heroin because doses are smaller than

t h e correagonding morphine or codeine doses, and are consequently cheape#,

a doctor who i s aware of h i s respons ib i l i t i e s , should not consider t h i s

a c t as su f f i c i en t j u s t i f i c a t i on fo r administering heroin in such,ala,rming

The Permanent Central Opium Board and t he Supervisory Body m u l d

consider it most des i rable t o have t h i s problem elucidated a s soon as

t h e 'WO Expert &omi t t ee , The supervision of in te rna t iona l

i n diacetylmorphine would thereby be g rea t l y f a c i l i t a t e d , and

t h e committees which a r e entrusted with t h i s t ask could only p ro f i t from

a serious study of t h i s question,

A s 2ub l i c h e a l t h problems are involvu-'. , t h e Oj3ium Board and t h e

Supervisory Body a r e agreed t h a t t h e ;MO Expert Committee shoulc' t a k e

c a r e of t h i s matter .

Avai lable i n fwmat ion proves beymc d a u l ~ t t h a t t h e use of

diacetylmorphine f o r rne$.ical purposes cannot be s o l e l y considered as a

sequel t o t h e war,

If t h e .vHO E q e r t Committee, a f t e r having t h o r ~ u g h l y examined t h e

problem of diace5ylmorphine,wre t o a r r i v e a t t h e conclusion t h a t bo th

from a medical p o i n t of view and from t h a t of pub l i c h e a l t h throughout

t h e world, it wou-ld be advisable t o completely e l imina te d i a ~ e t y l m o r p ~ l i n e ,

such a c snc lus i c~n i ~ ~ l d i ! be of t h e g r ~ a t c s t inq~or tance fc.r t h c afore-

mentioned con t ro l bodies . If one cons iders t h a t 25 S t a t e s m+ 27

T e r r i t o r i e s have a l r c a 2 y given up t h e use of diacetylmorphine f o r medical

p r p o s e s , such a recornmcndation by t h e Permanent Cent ra l 93ium Board

an2 t h e Supervisory Body would not seem t o o rnuch t o hope fo r . k

recommendation on t h e s e l i n e s had alrea6.y been presented as Resolu t ion 6

of t h e Convention of 1931, t h e t c x t of .~uhicf; fol lows:

"The Conference, r e c 9 g n i z i n ~ t h e h igh ly 2angerous cha rac t e r of

diacetylmorphine as a d r y ; of a d d i c t i o n and t h e p o s s i b i l i t y i n

m o s t , i f no t a l l , c a ses or" r e p l a c i n g it by o the r drugs of a

l<:;s dangerous cha rac t e r ;

R.3COMMENDS t h a t each government should 6xamine i n conjunct ion

1'3th t h e medical p ro fe s s ion t h e p o s s i b i l i t y of abol i sh ing o r

r ~ s t r i c t i n ~ y i t s lJSi?, an.? should communicate t h e r e s u l t s of such

examination t o t h e Secretary-General of t h e League of Nations.ff

If one t akes i n t o cons ide ra t ion t h e harm brciught about; fin t h e world

by diaadylmorphine s ince i t s appearance> and t h e thousands of he ro in

a d d i c t s who have f a l l e n v i c t ims t o t h e drug, t h e disappearance of

diacetylmorphine from world markets coulti only bc c..nsidered as a boon

and a s t e p i n t h e r i g h t ! i rcct ion, h~orecver , a complete ban on t h e

product ion of diacetylmor;3hine ~vould g r ~ a t l y facilitate t h e supe rv i s ion

of narcotj-CS, a s c o n t r o l bodies coulc! r i g h t l y c{)ncluc'.e t h a t hero in

discovered rin;rwhere i n t he world ciulcl only t o c~nt rakanc? , and even t h e

possess ion of t h i s dancerous p o d u c t m u l d c o n s t i t u t e an infr ingement of

c onvent ions.

I n order t o a t t a i n t h e requirec' g c s l - t h e cor;q)lete abcllit ion

of heroin - ~1 s c i e n t i f i c a l l y 3.12' , ~ s y c h o l o ~ i c a l l y ;?lnnncd ?r~;~aganr!a

cmi3aign s h o d ? be inauguratt;:! i.n -.rc?er t o c mvince c'octors ancl

governments the worlr' over t h a t t h e c ~mplo te abolj- t ion of 2i:-cetyl-

morphine i s an urzent necess i ty i n the s t r u c g l e t o c u r t a i l t h e use

.r)f dm;s which w e 2 menace t o public h e ~ l t h .

It woulcl k,c most d e s i r a t ~ l s th:it t h e iciO Expert Gommittee make

a stucly of t h i s ques t ion a t t h i s time, a s a new conventicm - t h e

f u t u r e Opium Convention - i s being dra~rm up and i s on t h e po in t of

being presented t o the var ious supervisory bo$.ies f o r nut o t i c s , and

t o governments.

t UNITED NATIONS NATIONS UNlES

W O R L D H E A L T H O R G A N I Z A T I O N

ORGANISATION 1ClOM)IALE DE LA SA-

WHO/HFD/~ Corr. 1 16 March 1949

ORIGINAL : ENGLISH

EXPEBT CObUITTEE ON HABIT-FORMING DRUGS

Report on the f i r s t session

Held 24-29 January 1949, Pa la i s des Nations, Geneva.

On page 7 amend item 1 0 (a) t o read a s follows:

(a) 3-hydroxy-N-me thy1 morphinan

The a t t en t ion of the Committee was drawn t o the f a c t t h a t German

and Swiss chemists have produced by d i r e c t synthesis a compound known

as 3-hydroxy-N-methyl morphinan, i n which the s t ruc ture of na tura l ly

occurring morphine a lkaloid has been nearly a t ta ined (R. Grewe, (1946)

Naturwissenschaf ten, 33, 333; (1947) ~ngew . Chem., 59, 194. The new - compound d i f f e r s from morphine chemically only i n the absence of t he

oxygen bridge and of the alcoholic hydroxyl i n posi t ion 6. It has

been shown i n the laboratory t o possess marked analgesic action,

greater than t h a t of morphine i t s e l f , and t o exh ib i t many of the other

charac te r i s t i cs of morphine action. ,

l The synthesis of 3-hydroxy-N-methyl morphinan i s d i f f i c u l t and a t

the moment probably not commercially feas ible . Nevertheless synthesis

of re la ted compounds i s going forward and the Committee i s of the

opinion t h a t progress i n t h i s f i e l d must be watched very carefully.