, National Institut United States Public Health Service, Washington (chairman)

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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 t h e f i r s t s e s s i o n Held 24-29 January 1949, P a l a i s des Nations, Geneva.

Members: D r . J. BOUQUET, Ex-Inspecteur des Pharmacies, Tunis D r . N. B. EDDY, P r i n c i p a l 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 D r . P.O. '#OLFF, Buenos Aires

Absent:Dr. H.P. CHU, Professor of Pharmacology, National College of Medicine, Shanghai

Secretary: Dr. R. MUTIER, A s s i s t a n t Director-General Observers: ilnr. V. PASTUHOV, Chief of Section, Division on

iVarcotics, United Nations

M r . A.E. FELKIN, S e c r e t a r y , 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 p a r t of t h e s e s s i o n (25-26 ~ a n u a r y ) i n h i s c a p a c i t y of member 01. the Permanent C e n t r a l Opium Board and of t h e Erug ~ u ~ e r v i s o & Body.

The agends having been adopted, D r . Eddy was e l e c t e d Chairman and D r . 1fJolff R a p p o r t w r

.

(2)

The question w h e t h e r , t h e preparati0.n .Valbinel was t o be exempted from t h e provisions of the 1925 Convention was discussed, s p e c i a l s t r e s s being l a i d on t h e content of dihydrooxycodeinone hydrochloride, t h e p o s s i b i l i t y of recovering t h i s alknLoid from t h e preparation, t h e 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 t h a t , taken s h d t a n e o u s l y : by,.bn addict, t h e y k dmaintain h i s s t a t e of addiction. ,

The following r e s o l u t i o n was passed:

, .

The Committee,

.

flaving considered a r e q u e s t from t h e French Goqernment t o have t h e preparationvValbine exempted from t h e provisions of t h e

.l925

Convention by a p p l i c a t i o n of i t s A r t i c l e 8, Is of' t h e o p i n i o n ' t h a t &eh exemption should not be granted

i n

favour of VaZbine# ,and

RECWNDS t h a t , t h i s d e c i s i o n be n o t i f i e d t o t h e Economic and Social, council of t h e United Nations f o r transmission t o thd French Government.

2. N o t i f i c a t i o n s 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 n o t i f i c a t i o n s from t h e gdvernments of t h e Unitec! ~ t a t e s ' o f America and of t h e United Kingdom a s t o t h e habit-forming p r o p e r t i e s of methyldihydromorphinone i d e

(Metopon HCl)

.

On t h e b a s i s of t h e observations made i n both t h e mentioned

c o u n t r i e s , t h e Committee adopted t h e following r e s o l u t i o n : .

-

^J

The Committee,

Having considered n o t i f i c a t i o n s from t h e Governments of t h e United S t a t e s of America and of t h e United Kingdom i n regard t o methyldihydr omorphinone hy2rochlor i d e (Metopon HC1) under

A r t i c l e 11 of t h e 1931 Convention,

. , ^a ^. Composition of Valbine? .

~ihydrooxycodeinane hydrchloride 1 mg

Phenylethylmalonylurea 3 CP

Extractum p i s c i 4 i a e ₂Cg Extractum pruni Virginianae'

3

C&'

Extracturn Crataegi 5 % ,

per, t a b l e t .

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Is of t h e o p i n i o n t h a t nLthjridihyc!rc noq7hinone and i t s s a l t s a r e habit-f orming d r u c s , anc!

RECOW~NDS t h a t t h i s o p i n i o n b e 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 p r o v i s i o n s of A r t i c l e 11, paragraphs 3 ^and

5

of t h e 1931 Convent i o n ,

N o t i f i c a t i o n r e c e i v e d from t h c Belgian Government re[;czr6ing 3 . ---.__ - . - - . - - -

-

^-_---.-^-^-^a^-^.^.^. ¹

a c e t y l d i h y d r o c o d e i n e h y d r o c h l o r i d c " G ~ ~ e ^_ ^_ ^l ^_ ^_name ^l : ^-hcetyicodone ^I--.I-,-.

--

^I_C--- ⁾

Tdz6;

- E u / I ~ P D / ~ )

The Comi:"ue has c o n s i c e r e d a n o t i f i c c t i o n r e c e i v e d 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 h a s no u p e c i f i c i n f o r m a t i o n on t h e habit,.foraing p r o p e r t y of ace2,yldihy(frococfeine, but i s of t h e opinion that, t h i s s u b s t a n c e i s c o n v e r t i b l e t o dihydrocodeine which, i? t u r n , i s

convex% Yule t o dihjdromorphine

,

^ah a b i t -f _o1:nin;i _drug, The s t a t e n e l l t w i t h r e s p e c 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 t h e 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 o p i n i o n 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 c o n v e r t j b l a t o dihydromorphine

,

a habit-f orming drug, should b e

c~mr~iunicated t o t h e Secretary--Generni of t h e United NaSi.ons.

4. P r o t o c o l s i g n e d i n P a r i s on 19 November 1948

W..---. __ .-..-.---_ ^-^.^v

The Committee no5cd t h a t t h i s P r o t o c o l , a l t h o u g h n o t h ~ j i.ng y e t r e c e i v e d t h e n e c e s s a r y number o f f i n a l s i g n a t u r e s , i s e x p e c t s ? t o

e n t e r i n t o f o r c e i n t h e v e r y nerw f u t u r e . Therefore, f o r p r a c t i c a l pwposes, t h e Cclr~mi.~tee d d c i d e d t o proceed a s i f t . h i n P r a t , o c o i were a c t u a l l y i n f o r c e ,

5, _{- "}¹^-7

-_-_-_

ethyl-4--p'henyl.i~ ""

_ -

fperidine-.4-.carboyylic

_

^_.-.^"-_ " _ _ - _ _

_____"

^--..._as "....~.^-..--"".n~U i d e t h y l ~ s t e r ^/..-A-

( t h e hydronhloridc of which i s known under t h e nrunes of.

D o l a n t i n , Demerol, P e t h i d i n e , PirS.dosa1, e t c , )

The Commitfee tms informed of t h e s t e p s t a k e n i n May 1945 b y t h e P r c s i d e n 5 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,

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

The Committee considered, however, t h a t t h e s u p e r v i s i o n t h u s e x e r c i s e d i s n o t 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 c o n t r o 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, o f t h e P r o t o c o l 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 a d d i c t i o n and should t h e r e f o r e f a l l under a r t i c l e 1, paragraph 2, Group I of t h e 1931 Convention, an8

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

General o f t h e United Nations.

6 , Other Substances o f the D o l a n t i n t y p e

.---v

-

A f t e r having exgrcssec! i t s opinion on l-methyl-4-phenyl- piperidine-4-carboxylic acid e t h y l e s t e r ( i t e m 5 ) ) t h e Committee b e l i e v e d t h a t t h e onus ^{was u2on} it t o c o n s i d e r a l s o t h e manjr o t h e r

s l ~ b s t q n c e s ~f s i m i l a r s t r u c t ~ ~ r e Itnorvn at p r e s e n t , and t,o r n i ~ i c k rcTerence i s made i n memoranda by Prof. F i s c h e r (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 , b e f o r e 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 a c i d 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 P r o t o c o l of 19 November 1948 comes i n h f o r c e , and RECOMMENDS t h a t t h i s opinion be n o t i f i e c ! t o t h e S e c r e t a r y - General of t h e United Nations,

--v.-

-- -

<-

-

See finnex l.

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

From t h e evidence before it,

The Committee is of t h e opinion t h a t t h e 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 d e f i n i t e l y be considered as habit-forming,3 and should be noted f o r a p p r o p r i a t e a c t i o n when t h e ,Protoco'l of 19 Moverhber 1948 comes i n t o f o r c e , and

RECOMMENDS t h a t t h i s opinion be n o t i f i e d t o t h e secretary- General of t h e United Nations,

8.

Precaut ioxxiry measures with regard t o ' s y n t h e t i c substances The Committee is of t h e opinion t h a t other compounds of a s t e u c t u r e similar t o those r e f e r r e d 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 p r o p e r t i e s u n t i l t h e c o n t r a r y be proved. The Committee considers t h a t governments shou3.d watch t h e s e compounds with extreme care and should t a k e a p p r o p r i a t e a c t i o n immediately on t h e discovery of t h e a d d i c t i n g p r o p e r t i e s of any one of them.

With r e f e r e n c e t o t h e experience a l r e a d y gained. with some members

of t h e Dolantin and Methadone groups, ⁱ

The Committee

REC-NDS t h a t provision should be made i n any new convention, whereby substances of a p a r t i c u l a r chemical type, analogues of

which have been proved t o b e habit-forming, could be placed under ^l c o n t r o 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 t h e views expressed by t h e Permanent

Ce Board and t h e Drug Supe B&y on t h e question of

3 s e e ~ n n o x ,?

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diacetylmorphine, consic?ered t h e i n c r c z s e 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 c o u n 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! b y t h e Committee o f E x p e r t s of t h e Conference f o r t h e L i m i t a t i o n of t h e

manufacture of n z r c o t i c dru;;s (1931), and which emphasized "the h i g h l y dangerous c h a r a c t e r of d i a c e t j l m o r p h i n e a s a drug of a d d i c t i o n and t h e g ~ s s i b i l i t y i n most, i f n o t a l l , c a s c s , of r e p l a c i n g it by o t h e r dru,;s of a l e s s eangerous c h a r a c t e r q ,

Having hearc! a s t a t e m e n t by P r o f e s s o r ~ 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 l a r m over t h e e x i s t i n g s i t u a t i o n ~ i t h r e g a r ? t o d i a c e t y l m o r p h i n e and s t r e s s e d t h e f a c t 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 d i a c e t y l m o r p h i n e i s n o t used a t a l l . 5

The Committee i s of t h e o p i n i o n t h a t f u r t h e r i n f o r m a t i o n i s urgent- l y needec? as t o t h e r e z s o n s governing t h e p r e s e n t use of d i a c e t y l m o r p h i n e i n some c o u n t r i e s , p a r t i c u l a r l y w i t h 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 s e c u r e 2 through t h e good o f f i c e s of t h e Yiorld Medical A s s o c i a t i o n , I n a d d i t i o n , d i r e c t i n q u i r i e s might b e

undertaken by t h e senc?.ing of a n 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 h i g h , i n o r d e r t o a s c e r t a i n from l o c a l p h y s i c i a n s anc? h o s p i t a l and s i c k n e s s i n s u r a n c e s e r v i c e s t h e r e a s o n s f o r t h e

p r e s c r i b i n g o f t h i s drug, The Fxpert Committee

EIECOm&NI)S t h a t s t e p s s h o u l d b e t a k e n t o s e c u r e i n f o r m a t i o n on t h e use o r d i s p t n s a b i l i t y of c ' i z c e t y l m o q ~ h i n c i n t h e v a r i o u s c s u n t r i e s through t h e d o r l d ldedical A s s o c i a t i o n and by sending m exL2ert t o c o u n 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

B u l g a r i a Greece Lwcemburg Polanc!

S p a i n

United S t a t e s of iimerica

Costa. R i c a Cuba

Dominican Ke;?ublic Guat ernala

Honcluras Nexico Nicaragua Salvador

B r a z i l C h i l e Colombia

Peru .

Venezuela China Japan

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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 ^;fthe US Public Haalth Service Hospital a&xington, Ky., USA, h s s carried ? u t t e s t s on the addiction

p o t e n t i a l i t y X' new s y n t h e t i c substances of t h e 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 t h e following, a s y e t unpublished:

1 l-methyl-4-metahydro~heny~-piperidine-4-carbo~lic acxd e t h y l e s t e r emid id one).

This substance i s p r a c t i c a l l y i d e n t i c a l with Demerol i n t h e reac- t i ~ n s which it produces and i n t h e dosage required t o praduce euphoria i n post-addicts o r t o supp-ess abstinence phenemena of an e s t a b l i s h e d mclrphine addiction. Its a d d i c t i o n p o t e n + , i a l i t y then i s 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 i n g l e dose, t h i s substance pr~duce:. in t e n s e euphoria i n former morphine a d d i c t s , It r e a d i l y suppresses abstinence phenomena of an e s t a b l i s h e d morphine addiction. The behaviour of men experi- mentally addicted t o Keto-Bemidone i s very s i m i 1 a ~ - + o t h e behaviour

of men addictad t o morphine. Tolerance develcped t s sedative a c t i o n , t h e e f f e c t on t h e e l e c t r c e n c e p h a l o ~ a m , th e erne%ic e f f e c t and t h e ef f e c t on the thermal r a d i a t i o n p a i n t h r e shald

.

Follonring abrupt withdrawal of Keto-Bemidone a f t e r a d a i n i s t r a t i s n f o r 42 t o 60 days,

an abstinence syndrome developed very r a p i d l y ( i n l e s s than 10 hours) which was so int;ense a s t o be regarded a s p o t e n t i a l l y dangerous ^GO l i f e , and which declined r a p i d l y .

The evidence i s unequivoc a1 %h :iL lie t =--Bemidone produce ^Sa 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 t h e mmphine s e r i e s and which i s S. g r e c t t h a t the drug s h ~ u l d n ? t be used i i i c l i n i c a l medi,-ine u n l e s s i t can be s h m n t o pnssess g r e a t advantage w e r t h e pqtent e ~ a l g a s i c s already a v a i l a b l e .

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 ^?filmi?rica m d t o t h e manuf3ccturers wh? h91d t h e

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'V\HO/APD/~

page 10

p a t e n t ln K e t il -2e;r,i4- nc

.

^{r ~ i e}l a t t e r h a ~ ~ r e 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 a n s 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--dimcthyl--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 h a n DemerQ i n t h e p r q d u c t i -n -f auph ) r * l a i n p > s t - r i d d i c t s and i n t h e s u p p e s s i o n c f 8.b- s t i n e n c c .;lf sri ? ~ t ~ i , ? ~ i ^{S'., ,d}:!,irphini, r ~ d d i c t i - ) n o The $--is-mer i s twice as. e f f e c t i v ; , t ~ c ;lfi-i S j~c>r t h r c , r f u r t i ~ n l s 2s e f f z c t j - v u es Dc.rnar~l

' i n t h e s s r t s p o c t s . %:fk, then: ;ri: c . a s l d e r e d t lir?.~.~e g r o c t o r a d d i c t i ~ n p:tcnti?Lity t h 2 n 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 ; u p h < x i a i n p x t - a d d j - c t s i n t b s d c s z s ~ d - i l i n i s t e ~ c l /9~-120 mg.), and h a s o n l y very s l i g h t e f f e c t t h c abstinen-lc 2henmena " m s s t z b l i s h e d mcirphinc a d d i c t i m . It

?ls> h a s v3ry wec?k :PC! act,i:n. I t s a d d i c t i n n p ~ t c n t i a l i t y a p p c z r s t:~ ba l w .

I n t h i s substirnce ^2.1hydrsxyl g 3 u p has bean a c a t y l a t d d as i n t h e change frr-,m m x p h i n e t o her.,in. I n csnsequznce a n d g c s i c a c t i ~ n hes bzen i n c r $ e s e d a t l e a s t 2s ~LLI::I ;is i n idethadene. The c~mpcund pr;- duces mnrkcd e ~ i i h x i e i n p m t - a d d i c Ls and re?.dil;y s u p p r e s s e s thd a b s t i n e n c e 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 d 2 s e s ceuse a s e v c r c t - x i c circul~.t-..1-;. r z c ? c l i f n . SwAl d . s z s rncrk~dly reduc; t h c i n t c ? n s i t y r f abstinunc;, pncn;me,.:,a )f m-.r.phind a d d i c t s , b u t " , ~ s z 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 r o n g ~ i c l 2 i c t i . n ? s t ~ n t i c ? ; l i t ; r , as grca:, , p r j b d ~ l y , as t h a t

(9)

ANNEX

I1

DUaTYLMORPHm (Heroin)

Memoranc?un by Professor H, Fischor

,The danger constituted by heroin i s nowadays undisputed*

Widespread heroin addiction i n New York between 1912 and 1920, and t h e perilous years between l 9 M and. 1930 i n Egypt ( ~ u s a e l l Pacha) a r e cases i n point, Because of few or inadequate control mea$ures, heroin production flourished, and i l l i c i t t r a d e i n t h i s product was exploited t o a remarkable degree of efficiency by contraband dealers, even aPter t h e e n t r y i n t o force of t h e Conventions of 1925 and 1 9 om t h a t time onwards, the unlawrul production of'herofn grewb and bounds i n China, p a r t l y with the help of European chemists. Ever increasing imports of a c e t i c anhydride were a clear ineication of t h e proportions a~stuned

i n

t h a t country by heroin product ion, which amounted t o dozens of tons per year.

The heroin smoking-habit introduced i n China was a p a r t i c u l a r l y pernicious form of heroin addiction ( nd, e t c, )

.

During t h i s period, t h e production of diacteylmorphine o s c i l l a t e d between 10, 20 and

X t o n s per year, It i s a known f a c t t t h e time of t h e Japanese invasion (1933 t o

1935)$

Japan made g

and Jehol with narcotics, including not only opiwn f o r smoking purposes, but a l s o heroin. During the second. world war, Japan used heroin as a weapon i n carrying out i t s genocidal policy 5x1 Ihnchukuo, You w i l l no

,

doubt r e c d l t h e Mulcd.cn factory, whose production of diacety'lmorphine reached 50 tons annually.

1% would seem l o g i c a l t o completely ban t h e use of a poisonous drug which has wreaked such havoc throughout t h e world during t h e l a s t 50 years. The Convention of 1931 was designed f o r t h i s purpose, but only a few countries adhered t o i t s s t i p u l a t i o n s , In t h i s regard t h e Unitec?

S t a t e s has scrupulously c a r r i e d out i t s obligations f o r 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}f u l f i l t h e same purposes, and it should at l e a s t haGe d e f i n i t e therapeutic

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q ~ m l i t i e s . I n my opinion, none cf t h e aforeraent ioned c o n d i t i o n s 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 , h e r o i n i s g s n e r a l l y cunsiclered a s an

extremely c'angerous dru,

.

J14ost d g c 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 u s i n g it, and ~vould no 9 u b t a g r e e t o i t s c9~mnplete e l i m i n a t i o n

t k r o u t t l o u t t h e ^{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 b o t h anomalous and d i s q u i e t i n g , I n c e r t a i n c c u n t r i e g

,

d o c t ~ r s a r e ; r e s c r i l ~ i n g h c r o i n vvith e v e r

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 i s c a u s e f o r alarm.

For d o c t o r s , t h e i n c r e a s e d use of h e r o i n i n v a r i o u s c o u n 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 i s unanimous a s t o t h e harmful n a t u r e of h e r o i n , b o t h from e medical and n a r c o t i c viewpoint.

A s

G e n e r a l l y speaking, d i a c o t y l n o r p h i n e i s more t o x i c t h a n morphine, a s t h e r e s u l . t a n t a n a l g e s 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 s e d a t i v e and ; 7 a r a l y t i c 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 h a n 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 r e s c r i b e d 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 c p , n d i t i m s , i n c l u d i n g t h o s c c a u s i q ; 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 h o s c 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 l a r y n x , Diacetylm3rphine i s c ~ n t r a - i n e i c n t e d when dealin; w i t h emphysema, asthma and h e a r t t r o u b l e .

The e l i m i n a t i o n o f h e r o i n i s c ' i r e c t l y r e l a t e d t o t h e p r c s c r i ; ? t i o n s made by d o c t o r s . Heroin c a n bc p r e s c r i b e ? f c r cough c o n d i t i c n s and i r r i t a t i s n s ir, t h e r e s ; ) i r 2 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 c a s e s of t u b e r c u l o s i s o f t h e larynx, b u t t o a l e s s e r d e g r e e as a c e n t r a l a n a l g e s i c , I n o t h e r words, t h e s 2 s c i f i c medical u s e s of ?.iacetxlrndrphine a r e n o t t o be d i s t i n g u i s h e d from t h o s e of o t h e r

. .

a n a l g e s i c s used i n cau?,h conclitions, such a s mor2hine, a c e ~ , ~ c J L , ~ , G U ~ U L ~ L ~

d i l n u d i d e , pernonide, and dicoc?ide,

A s a ct3uch remedy, t h e r e i s consequently no medical j u s t i f i c a t i o n f o r * > r e f e r r i n g d i a c e t y l m o r g h i n e t o o t h e r dru; s , o r of even p l a c i q g it i n

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wo/m/9

page 13

t h e same category, Possible r e p e r ~ u s s i o n s on t h e r e s p i r a t o r y t r a c t and t h e ease and r a p i d i t y with which a d d i c t i o n can be acquired, a r e f a c t o r s which c l e a r l y i n d i c a t e t h a t it cannot be considered as u s e f u l a s t h e above-xpentioned drugs,

A s i s i n d i c a t e d i n t h e r e p o r t submitted by t h e Permanent 0entra.l

Opium Board t o the S o c i a l and Zonomic Council on t h e work a c ~ ~ ~ l ~ ~ i i s h e d by t h e Board i n 1948, t h e r e are f i v e c o u n t r i e s whose consumption of

ylmorphine reached 2 kg, p e r m i l l i o n i n h a b i t a n t s and f i v e a t h e r i e s where over 5 kg

.

x e r e consumed. By o r d e r of h i g h e s t con- sqt ion, %hese c o u n t r i e s a r e : Italy, New Zealand, Sweden, A u s t r a l i a , and CanaCla, One country inland) uses more t h a n 25 kg

.

of d i a c e t y l - morphine per m i l l i o n i n h a b i t a n t s , I n c o n t r a s t , among t h e 74 c o u n t r i e s 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 n o t made p r o v i s i o n f o r d i a c e t

The following are some of t h e countr tylmorphine : United S t a t e s , Japan, Austria, Bulgaria, Hungary, Spain, Poland, Mexico, B r a z 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 t s present programme of work t h e question of diacetylmorphine, which i s a matter of s e r i o u s concern t o t h e Permanent

Opium Board a s well a s t h e Drug Supervisory Body, Neither t h e n t Central

9 i u m

Board nor t h e Supervisory Body s e e s t h e n e c e s s i t y or even t h e u t i l i t y of increasing t h e consumption of heroin i n Finland, I t a l y and other c o u n t r i e s , f o r reasons which have been put forward b y cJoctors i n those c o u n t r i e s . Lf, i n Finland, s i c k n e s s insurance

organizations encourage t h e use o f heroin because doses a r e smaller t h a n t h e correagonding morphine or codeine doses, and are consequently cheape#, a doctor who i s aware of h i s r e s p o n s i b i l i t i e s , should not consider t h i s

a c t as s u f f i c i e n t j u s t i f i c a t i o n f o r administering heroin in such,ala,rming

The Permanent Central Opium Board and t h e Supervisory Body m u l d consider it most d e s i r a b l e t o have t h i s problem e l u c i d a t e d a s soon as

t h e 'WO Expert & o m i t t e e , The supervision of i n t e r n a t i o n a l i n diacetylmorphine would thereby be g r e a t l y f a c i l i t a t e d , and t h e committees which a r e e n t r u s t e d with t h i s t a s k could only p r o f i t from a serious study of t h i s question,

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A s 2 u b l i c h e a l t h problems are involvu-'.

,

t h e Oj3ium Board and t h e S u p e r v i s o r y 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 m a t t e r .

A v a i l a b l e i n f w m a t i o n proves b e y m c d a u l ~ t t h a t t h e u s e of

diacetylmorphine f o r rne$.ical purposes cannot be s o l e l y c o n s i d e r e d as a s e q u e l 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 d i a c e 5 y l m o r p h i n e , w r e t o a r r i v e a t t h e c o n c l u s i o n t h a t b o t h from a medical p o i n t of view and from t h a t o f p u b l i c h e a l t h throughout

t h e world, it wou-ld b e a d v i s a b l e t o completely e l i m i n a t e d i a ~ e t y l m o r p ~ l i n e , such a c s n c l u s i c ~ n ⁱ ^~ ^~ ^l ^d ⁱb e of t h e g r ~ a t c s t ^! i n q ~ o r t a n c e fc.r t h c afore-

mentioned c o n t r o l b o d i e s . If one c o n s i d e r s 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 g i v e n 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 C e n t r a l 93ium Board a n 2 t h e Supervisory Body would n o t seem t o o rnuch t o hope f o r . k

recommendation on t h e s e l i n e s had alrea6.y been p r e s e n t e d as R e s o l u t i o n

6

of t h e Convention o f 1931, t h e t c x t of .~uhicf; fo l l o w s :

"The Conference, r e c 9 g n i z i n ~ t h e h i g h l y 2angerous c h a r a c 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 n o t a l l , c a s e s or" r e p l a c i n g it by o t h e r drugs o f a l<:;s dangerous c h a r a c t e r ;

R.3COMMENDS t h a t each government should 6xamine i n c o n j u n c t i o n 1'3th t h e medical p r o f e s s i o n t h e p o s s i b i l i t y of a b o l i s h i n g 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 a k e s i n t o c o n s i d e r a t i o n t h e harm brciught about; fin t h e world by diaadylmorphine s i n c e i t s appearance> and t h e thousands of h e r o i n a d d i c t s who have f a l l e n v i c t i m s t o t h e drug, t h e disappearance of diacetylmorphine from world markets coulti o n l y bc c..nsidered as a boon and a s t e p i n t h e r i g h t ! i r c c t i o n , h ~ o r e c v e r , a complete ban on t h e p r o d u c t i o n of diacetylmor;3hine ~vould g r ~ a t l y facilitate t h e s u p e r v i s i o n of narcotj-CS, a s c o n t r o l b o d i e s coulc! r i g h t l y c{)ncluc'.e t h a t h e r o i n d i s c o v e r e d rin;rwhere i n t h e w o r l d ciulcl o n l y t o c ~ n t r a k a n c ? , and even t h e p o s s e s s i o n 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 i n f r i n g e m e n t of c onvent ions.

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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 abcllition of h e r o i n

-

^~1s 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 m v i n c e c'octors ancl governments t h e worlr' over t h a t t h e c ~ m p l o t e a b o l j - t i o n of 2i:-cetyl- morphine i s an u r z e n t n e c e s s i t y i n the s t r u c g l e t o c u r t a i l t h e u s e .r)f dm;s which w e 2 menace t o p u b l i c 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 E x p e r t Gommittee make a stucly of t h i s q u e s t i o n 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 p o i n t of being p r e s e n t e d t o t h e v a r i o u s s u p e r v i s o r y bo$.ies f o r nut o t i c s , and t o governments.

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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 t h e f i r s t s e s s i o n

Held 24-29 January 1949, P a l a 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 e n t i o n of t h e Committee was drawn t o t h e f a c t t h a t German and Swiss chemists have produced by d i r e c t s y n t h e s i s a compound known as 3-hydroxy-N-methyl morphinan, i n which t h e s t r u c t u r e of n a t u r a l l y occurring morphine a l k a l o i d has been n e a r l y a t t a i n e d (R. Grewe, (1946) Naturwissenschaf ten,

_-

33, 333; (1947) ~ n g e w

.

^Chem., ^{5 9 ,}^194. ^{The new}

compound d i f f e r s from morphine chemically only i n the absence of t h e oxygen bridge and of t h e a l c o h o l i c hydroxyl i n p o s i t i o n 6. It has been shown i n t h e l a b o r a t o r y t o possess marked analgesic a c t i o n ,

g r e a t e r than t h a t of morphine i t s e l f , and t o e x h i b i t many of the o t h e r

c h a r a c t e r i s t i c s of morphine a c t i o n . ,

l

The s y n t h e s i s of 3-hydroxy-N-methyl morphinan i s d i f f i c u l t and a t t h e moment probably n o t commercially f e a s i b l e . Nevertheless s y n t h e s i s of r e l a t e d compounds i s going forward and t h e Committee i s of t h e opinion t h a t progress i n t h i s f i e l d must be watched very c a r e f u l l y .