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CLASSICS RE VISITED

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Uber Coca: Freuds Cocaine Discoveries

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EDITORS I STRODUCTIOS
R E G A RDL E S S OF TXE ~DJ-ECTWES used to describe contemporary cocaine use and/or abuse, the trend toward increased and more widespread use h2s been well documented (e._e., Gold, 19s;). The history of cocaine goes back more than a millennium t o the early use of the coca plant (Erthroxylon coca) in South America. Dyke (1981) suggests that the reasons for the early practice of chening the coca plant leaves have been lost in antiquity, but that there is evidence from Indian burial sites thzt this activity began before the 6th century AD. Dyke also notes that the coca leaves were considered precious and were usually reserved for nobility and religious ceremonies (1981, p. 158). Presently, it is estimated that over 4 million Peruvian and Bolivian Indians chew coca leaves regularly (Dyke, 1981). Even though chewing the coca leaf could produce euphoria, this activity was not as popular in Europe as drinking tea or coffee, perhaps, Dyke (1981) suggests, because the leaves deteriorated during the long voyzges between Sourh America and Europe. In IS55 Gzrdeke was the first t o extract the active ingredient of the coca leaf, which he called erythroxylon. According to Byck (1974), Niemann isolated the alkaloid 5 years later and named it cocaine. Once this psychoactive ingredient was isolated, there was a great flourish of personal experience and sc.ien1ific experimentation with the substance. Sigmund Freud, the father of psychoanalysis, was initially responsible for the medical, scientific, and personal interest espressed by many of those who studied and used cocaine since Ihe nineteenth century. In fact, Freuds work, Uber Cortl, has been considered ! o be the definitive description of the effects o f cozaine in hzrr.sr.s(Dyke, 19S1, p. 159) and renccis the history of the study and use of cocaine from the middle to the end of the nineteenth century. Freud began his work with cocaine while he was a house officer at the lienna General Hospital. His firsi reference IO cocaine w3s expressed in a letter nritcen on April 21, 16S1 I O his fiancrc .\lartha Ber-

n a y Ishen he identified a therapeutic project and a hope (Byck, 1974, p. 5).

I have been reading about co;air:e. ihc essential c0ns:ituent of coca leaves which some I n d i a tribes chew to en?Slc them to resist privations and hardshjps. .4 Gcmm h r s S t e n emplojing it with soldiers and has in f2ct reponed ;h2t ir increzses their energy and capacity to endure. I am procuring some myself and will try it with cases of heart diseve and also of nervous exhaustion, particularly in the miserable condition after the wirhdraud of morphium . . Perhzps

others are working at it; perhaps nothing will come of it. But I shall certainly try it, end yo^ know that when one perseveres, sooner or later one succeeds. (Byck, 1974. pp.
5-6)

This letter indicates several things about Freud and the context in which he worked. First, it reflecrs the passion and achievement motivation thzt energized his creative life. Second, it hints at the willingness of Freud to fail, persevere, and ultimztcly succeed at an endeavor that had little p s i l i v e consequence nuaranteed. In addition, this letter reflects the lack of regulation surrounding rhe use of cocaine as well 2 s the standard medical practice of that time for physicians to use and experiment uirh the drugs that they were studying or prescribing. Finally, Freuds willingness to experiment personally \vith cocaine indicares that he did not consider the drug experience 2s discontinuous from the rest of his life; perhaps, with his willingness to alter his own consciousness and accept the potential risks inherent to this experience, Freud was, unknowingly, lsyicg the subjective ground\vork for his conceptual development of the unconscious. Uficr Cu;a d<:s:rlbtj : : histor)., phzrmacology, h animal and human effects. as \\ell as the medicinal applications of cocaine. Although Freud d x r i b e d a variety of medical applications for cocaine, ir \vas onlp later. in an addenda to this paper. that he considered s he anestSetic properties of the substance 2nd its a g plication for eye surgcry. Consequently, Karl Kollcr, a colleague of Freud. is considered by most sources to be the dirco\,erer of local anc~ihesi3 B ~ c k .1974). (

C bcr Coco srands 2s a beacon to the understanding of cocaine and its nztural history \rithin a social and scientific col;test t h a t \vas essentially unregulated. and rherefore; not influenced by government intertmtion. I n addition. Uber Coco illustrates the naive tendency of some energetic in\.esligators to believe that it is possi'clc I O "cure" chemkal dcpendcncy to one drug simply by substituting another, i.e., treatiny the s y m p ton:s of morphine and alcohol dependence with cociine. Freud displayed similar naivete- as h a \ e scores of other clinicians- by not recognizing the insidicus 2nd potent abuse potential of cocaine. Ye\.errhelcss, Freud's analysis of the psychological 2nd ~\hysiolo~i~rl effects of cocaine remain as iriforr n Z t i \ e End precise 2 s \\hen thes: de$criptiox \\ere o-;r:F* .,=.,.-!Iy formulaitcl. A s a result, Frtgd ~ z n

Uber Coca
SIGMVSD REUD F
I. T h e Coca Plant

The coc2 plant, Eryd-uoxylon coca, is a bush four to six'fect in height, similar io our blackthorn. It is culti\.ated extensively in South America, in p a n i c u i v in Peru znd Bolivia. It thrives best in the u'2rm valleys o n the a t e r n slopes of h e Andes, 5000-6000 feet above sea level, in a rainy climate free from extremes of temperature.' The leaves, which provide 2n indispens2Slc stjmulant for some 10 million people,' 2rc egg-shaped, 5-6 cm long, stalked, undivided, and pruinose. They arc distinguished by two linear folds, especially prominent o n the lo\vtr surface of the leaf, which, Like lateral nerves, run along the medial nerve from the b u e of the leaf to its point in a flat arc: T h e bush b a r s small white flowers in lateral clusters of two or three, a n d produces red egg-shaped fruits. It can be propagated either by seed o r by cuttings; the young plants are transplznted after a year and yield their first crop of leaves aft& eighteen months. T h e

leaves are considered ripe when they h i v e become so stiff that their stalks b i e k upon being toached. They 2re th:n dried r i ~ i d l y ,eirhtr in the sun or u i t h the ai3 of fire, and into szcks (cesros) for transpon. In favorable conditions a coca bush yields four or five leaf crops annuzlly and will continue to produce a yield for between thiny and f o n y yezrs. T h e large-sczle production (allesedly 30 million pounds annually) makes coca leaves zn imporant item of trade and raxarion in the countries where they are grown.'
11. The Hislory and Countn of Origin

Uses of Coca i n its

'I o w this docription I O Professor Vogl of Vicnna. uho h u most kindly placed his notes and books oboui coca ai my disposal.
"i)ber Coco.' Yon D r . Sigm. Freud, Pcundororft im k.k. Allpemrincn Krcnkcnhorrtc in H'ien. Ceniralblorr f u r die t . u Thcropie. 2 , 389-314. 1864 Juli.

On C o a . By Dr. Sigmund Freud, house officer of the Gcnc:aI

Hospi:rl of Vienna. T:rnslaied by Steven A. Edminsier; addjiions I O the irans!s:ion by Frcocrick C. Rcdlich. Rc?:i:.:cl from Cocsinr Pipers (19:z). R . B y i k (Ed.). S:on:t,ill PuS:st.ing C o n p m y . Xcu I'o:L.

\Vhen the Spanish conquerors forced their way into Peru they found that ihe coca plant w a cultivated and held in high esteem in thzt country; and indeed that it was closcly connected uith the religious cUStoms of the people. Legend held that Manco Capac, the divine son of the Sun, had descended in pirnevd times from the cliffs of Lake Titicaca, bringkg h 5 father's light to the wretched inhabitants of the country; that he had brought them knowledge of the gods, taught them the useful 2m, 2nd given them the coca I d , this divine plant whjch satiates the hungry, strengthens the weak, and causes them to forget their misfortune: Coca leaves were offered in sacrifice 10 the gods, .\\'ere chewed during religiou~ceremonies, and were even placed in the mouths of the dead in order to assure them of a fa\*orablere:ep:ion in I h c be\ond. The hir;orizn of ;he Spanish C O ~ O ' J C ! ~ . ' bairn-

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sclf a dcsccndant of the Incas. reports that coca was

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first a scarce commodity in the land a n d its use a prerogative of the rulers; by2he time of the conquest, ho\vc\.er, i t had long since become acccssiblc to c\'cryonc. Gzrcilzsso endeavored to defend coca against the ban which the conquerors laid upon i t . T h e S p a n i u d s did not believe in the marvelous cffccts of the plant, which they suspected as [he work of the det-il, mainly bccause of t h e role which it played in the religious ceremonial. A council held in Lima went so far as to prohibit the use o f the plznt o n the g r o u n d that it was heathenish a n d sinful. Their attitude changed, however, when they observed that t h e Indians could not perform t h e heayy labor imposed upon them in the mines if they u e r e forbidden to parteke of cocz. They compromised to the extent of 6is:riburing coca leak-es io the workers three or f o u r times daily and allowing them shorL periods of respite in which to chew the beloved leaves. And so t h e coca plant has mzintained its position among [he nz:i:.es to ihc present day; there even remziil tr2ces cf !he religious vcnerztion u h i c h was once accorded to it.* T h e Zndjzn alu,ays carries a bundle of coca leaves (c211e3 chwpa) on his wanderings, a s well as a bottle conrzinir.? plant esh (Ncru).' I n his m o u t h he forms rhe lezvts into a b2U, which he pierces several times Lvir'n 2 thorn dipped' in the u h , a n d chews slowly a n d thoroughly wirh copious secretion o f saliva. It is said o that i n other areas a kind of c a n h , ronro, is added i the leaves in place of the plant ash.' It is not considered immoderate to chew from three IO four ounces of leaves daily. According to 'Mantegazza, the Indian begins to use this stimulant .in early youth a n d continues 10 use it throughout his life. %n h 'e h e is faced \vith a difficult journey, w h r n he takes a woman, or, in g e n e i d , \\-henever his strength is m o r e t h a n usua!ly taxed, h e increases the customary dose. (11 is not clezr what purpose is achieved through ihe admixture of the alkalis contained i n the ash. blantegazza claims to have chewed coca leaves both \vith a n d \vithout Nicro and to have noticed n o difference. .Axo:lizg I O .\.!artius'O a n d Demarle,l' the cocaine. probably held in compound tvith tannic acid, is released by the action of t h e alkalis. A Ilicfa 2nal!.zed by Bibra consisted of 29To carbonate of lime a n d magnesia, 3 4 r o potassium salts, 307, zrgillaceous ezrrh and iron, 17010 . insoluble compounds of zrgillaceous earth. siliceous earth a n d iron, 5?0 carbon and 10To water.) There is ample evidence that Indians under the influence o f coca .can withstand exceptional hardships 2nd perform heavy labor, without n c r u r i s h r m t during that time." Valdez y c!sims th21 by using coca the Indians are able to [ : ~ \ ' c I a n foot for hundreds @ ihours a n d run faster 1!-1an horses \tii!-iOut shc\ting signs of

nau," Alartius," 2nd Scrit'cnc:" confirm [his, and Humboldt spcaks of i t in connection with his trip to the equatorial regions as a generally kno\\n fact. Often quoted is Tschudi's" report concerning (he performance of a cholo (half-brced) whom he was able to observe clostly. T h e m2n in qucstion carried out laborious cxca\,ation work for five days and nights, without sleeping more than tueo hours each night, and consumed nothing but coca. Aftcr the work was completed he accompm'ed. Tschudi o n a two-day ride, running alongside his mule. He ga\'e \ every assurance that he would gladly perform the Same H.ork again. without er:ing, i f he were gi\-en enough coca. T h e man was sixty-tu.0 years old zn;! had never been ill. In the / o u r m y of the Frigc:? '.~'OI.C~;', sinilzr examples are recounted of incicrsed physic21 powcrs resulting from Ihe use of coca. \\'e3dell," \.on >leycn," hlzrkham.'O a n d eves Poeppig" (whom \ve have :o thank f o r many o :he sl.?i~derousrepor:s f &out coca) can only confirm this cffecr of the leaf, which, since it first became knau.2, !?: ci?n!ir,.u:d : o be a source of astonishment thiouchoilt the world. Other reporrs stress the czpacity of the coqueros (coca chewers) to abstain from iood for long periods of time without suffering any ill effects. According to Unanut,12 when n o food w a s a v d a b l c in the besieged city of La Paz in the year 1781, only those inhabitants sur\ived who p a r t o o k of coca. According to Stewcnson," the inhabitanrs o f many districts of Peru f 2 r r , sometimes for days, a n d mith the aid of coca are still able to continue working. In view of 211 this evidence, and bearing in mind the role which coca has played for centuries in South America, o n e m u s t reject the v!e\v sometimes ex. pxssed, that the eifect of coca is an irnaginzry one and that through force of circumstznccs 2nd with practice the natives would be zble to perform the feats attributed to them even without the aid of coca. One might expect to learn thzt the coqueros compensate for abstention from food by eating correspond. ingly more during t h e inrervals bctucen their fasts, or that as a result o f their mode cjf life they fall into a rapid decline. T h e reports of rrivelers on the formrr point are not conclusive; as foi t h e latrcr. i t has been denied emphatically by reliable witnesses. To be sure, Poeppig painted a terrible picture of thc physical a n d intellectual decadence which are supposed to be [he inc~itablc conscquencc of the hzbitual use of coca. But all other observcrszffirrn t:;zt t h e use of coca i n moderation is m o r e likely to ?;omore health thzn 10 impair i t , and that the eddcll and

apathy to\rzrd c\r.:!ihins

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i h e znjo! inen1 o f t h e siirnu1:nt. \\'hit$ p o p l e sometimes succumb as \tell to Ih:s state, \\liich bears a g r e a t similarity to the symploms of chronic alcoholism and morphine addiction: I t is notncc:r.d
ii h

IzLcn i n \\holly immoderate quzntilies; and ne\er f:om a presumpii\.e disproportion beineen the zrnouni of nouiishmcnl taken and the 2mount of N ork performed by the c~qrreroS.
I

i l l . C o c a Le3t.e~in Europe- Cocaine

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,~ccording I O Do\vdes\vell," the earliest recommcndzrion for coca is contained in an essay by Dr. \lona:des (SeL ille. 1569) \vhich appeared in English trznslaiioii in 1535. Like the lzrer ieports of t h ~ J e i u i r Fither .Ar.tonio Julian," znd the docior Pedro Creipo.:' both of Lima, 3lonardes' esszy estols tne mzrvelous effect of the plant in combating hunger an3 fatigue. Both of the former authors had _eretit hopes for the iniroducrjon of coca into Europe. In IS49 the p i m t brought to Europe; ir was describcd by X.L. de Jussicu and clzcsed \vith the nen!is Erythrosylon. In 1786 it appezred in Lamzrck's 1;cylopidie .kfirhodique Boranique under the name of Erj.fhroxjlon coca. Reports of travelers such as T s h a i and 31xkham, among others, pro\ided proof ihat the eifcst of coca leaves is not confined to the Indim race. In 1659, Paolo Manteguza, who had lived for a number of years in South America's coca regions, published his discoveries about the physiological and iherrpcutic effecu of coca leaves in borh hcmispheres2' 3 l a n t e g u z a is an enthusiastic eulogist of coca and illustrated the versatility of its therapeutic uses i n reports of case histories. His report aroused much inrcrert but little confidence. Howver, I have come across so many correct obscwations in Manicg w ' s publication that I am inclined I O accept his allegations even when I have not personally had a;l opportunity to confirm them. In 1859. Dr. Scherrer, a member of the expedition in the Austrian frigate Novuru, brought a batch of coca leaves 10 Vierma, some of which he sent to Professor Wohler for examination. Wohlcr's pupil N e mann2' isolated the alkaloid cocaine from them. After Niemann's death, Lossen,'O another pupil of U'ohler, 'continued the investigation of the substances contained in coca lea\*es. * M e m a n ' s cocaine crystallizes in large, colorless, 4-6-sided prisms of the monoclinic type. It has a somewhzt bitter taste and produces an anesthetic cffect on the mucous membranes. It melts ai a temperature of 96'C. is difficult to dissolve in water. but is
'There is \*cryliiilc rprecmcni among authors about the ro1ubili:y of co-aine in u-rier. 11 is evident that various prepzationr of ' e : ciin:" c z m c o n the marlci and ucrc b:oughi inio use.

marle ( I 862), Gosses monograph on Eryhroxylon coca ( I 862), Reiss ( 1 866) Lippmanns rude f u r la coca dir PProu (1 868). MorCno y Mdiz (1 668), w h o pro\,ided certain new facts about cocaine, Gazeau ( 1 870). Collins (1S77), and Marvaud in the book L a olimznrs deporgne (1671), the only of the above essays at my disposal. In Russia Nikolsky, Danini (1673). and Tarkhanov ( 1 S72) concentrated particularly on studying the effects of cocaine o n animals. hlany reports, all of which have been published in the Detroit Therapeuric Gazerre, have emerged from North America in recent ycars on the scccessful therapeutic use of coc.5ae preparations. T h e earlier of the investigations referred to here led, on the u,hole, to great disillusionment and to the con\.iciion that effects from the use of coca such 2s had been reporred so enthusiastical!y from South .qmeiica could not be expected in Europe. Investi_eations such 2s those carried out by Schroff, Fronmuller, a n d Dowdeswell produced either negative or, 2t the most, insignificent results. There is more than one esplanztion f o r these failures. Certainly the quzliiy of the prepzrations used u a s largely to blame.? I n a number o f cases the authors themselves doubt as to > t h e quality of their preparations; a n d to the extent that they believe the reports of travelers o n the effecis cf coca, they assume that these effects must be attributed to a volatile component of the leaf. They base \this assumption o n the report of Poeppig, a m o n g others, that even in South America lezves which have been stored for a long t i n e 2re considered ivonhless. T h e experiments carried out recently with the cocaine prepared b y 3lerk [sic] in Darmstadt alone justify the claim that cociine is the true agent of thc coc2 effect, which can b e produced just as well in Europe a s in S o u t h A m e i i a and turned to Qoodaccount in diete;ic a n d therapeutic rreatment.
I\. The Effect of Coca on Animals

\\*e kno\v that animals of different species- and even individGz!s of the same species- differ most markedly from o n e another in those chemical characteristics ivhich determine the orgznisms receptivity to foreign substances: \!e would, therefore, as a matter of course, not espect to find that the effect of coca o n znimals in zny way resembled the effects ivhich it has been described to h2ve on man. \Ye m s y be satisfied n i t h the results of o u r inquiry I O the extent that \ \ e

can ccmprehcnd the way cocaine affects b@:h m a n and animals from a unified standpoint. We a r e indebted to von Anrep for t h e most exhaustive experiments regarding the effects o i coca o n animals. Before him. such csperiments NC:C cariicd out by Schroff senior, 3lorcno y 31212,~ Tzrkhanov, Nikolsky.J6 Danini, A . B:nneit, and Ott.* The majority of these authors introduced [he alkaloid either orally or subcutzneously. The most general result of such experiments i that, in small doses, coca has a stimulating, and in larger doses a paralyzing, effect on the nervous syst e n . In the case of cold-blooded 2nirr.23 tht,pz;aIyzing effect is particularly noticeable, while in jvarmblooded animals symptoms of stimvlirion are the mosr apparent. According to Schroff, coczine p r o d x e s i n frcgs a soporific condition accompenied by p2rAysiz of the voluntzry muscles. hloreno ! 5laiz, Dznini, Siko!sky, and Ott made fundamental!y the s2mc disco\,eiv; Sforeno y Maiz alleges [hat the general pzralysis ensuing from moderats doses is preceded 5y r::znus; under the s a n e conditions S i k c l s k y describes i j:ige of escitation of the muscular system, w.hi;e Dtnini, on the other hand, never observed a r , spzsms. \on Anrep likewise reports a p2ralyzing effect of cocaine o n frogs after a short period of es5:Z:ion. .4r first the sensory nerve endings 2nd later t h t sensory nerves rhemsclves a r e affected; breathing is at first accelerated and then brought to 2 standstil!; 2nd the functioning of the heart is slowed down until the point o f diastolic failure is reached. Doses of 2mg suffice to provoke symptoms of poisoning. -4ccording to Schroffs accounts of his esperiments with rabbi!s (Lvhich in dttril z:e fr2nS:St n:i!h contradictions), coca produces mu!Lipl: s p s m s in rzbbits, increased respiratioa and pulst rzie, dilziion of the pupils, and convulsive death. Th: effexiveness of the poisoning depended to a large es:eni on the mode o f application. According IO Dznini, cocaine poisoning in \varm-b!ooded animals produce! 21 iirst agitation, ivhich manifesrs i:self in con:inuoas j z m p ins and running, then paralysis of the T.Gs:~!z: fcnctions, a n d finally spasmodic (clonic) c r z y p . T i r k hanov discovered a n increzss of mucous secretion i n dogs dosed \vith coca, and also sugar ir t h e u r i n e . In von Anreps espsriments, the cficcr of cocaine, even in large doses. on \\.zrm-bloodsd znimzls manifested itself first of all in po\\eriiil psychic agiration and an escitation of the brain ccnlers \\ h i i h c o x r o l voluntary movement. Afrcr doses of 0.01g of cocaine per kg. dogs shot\. ob\-ious signs of h a p p y excircment and a maniacal compulsion 10 rn3i.e. F r o n [ h e c h a r actcr of t!ic,c rno\emcn;s \cn .-\nrsp s c t j c\id:nce i h 3 t all ncr\e ;cnir.rs a r c af<cc;cd t t ! siimu:a!iL-n. ~ . .y 2nd hr. inicrprc:s Ccrl3i;; i:\ing:ng : s s : i ~ n s C i ! l C ti233 A j 2;) i:ri13:i.T? pr,-:c:d:ns i:,-n; !F.c

<::cc!zr c z n ~ l s .Furthcr m3nifc~t3tior8s cocaine inof ioxicition are accclcraied rcrpiraiion. a great increase in the pulse raie owing I O early paralysis of Ihc 8 . \ h g i . dilation of the pupils, 2n accelcration of intc5tinaI mo\.emcni, a great increase in bloodpressure, and diminution of secrerions. E \ r n after d c e s large er,ou_ch to produce eventual coniulsions. s\ mproins of paralysis and deaih due to paral).sis of rhe respiraiory ientcr, the striated muscle substance remains intact. \'on .%nrep does not establish the leiha1 dose for dogs; for rabbits i t is 0.10s and for C 3 I S 0.02s per k_p: \\'hen :!IC spins1 cord is se\.cred from the oblons e t a . cocaine produces neither cramps nor a rise in blood-prssure [Drnini); when the dorsal portion cf t i e 5pir.sl cnrd is severed. cocaine spasms occur in t5e ironr bur not in the rear extremities (von Anrep). Dznini and \'on X n r e p assume, therefore, that cocrine zffccts primarily the virrl 2rea of the medullz
o?.lcn_cz:a.

I shocl3 add thzr only the elder Schroff refers t o c x a i n c 2 s a nzrcotic and clacscs it ivith opium a d crnnabis. while almost everyone else ranks it with caffeinc, erc. Y . The Effect of Coca on the Nealthy H u m a n Body
I have carried out experiments a n d studied, in myself and o)hers, the effect o f coca o n the healthy human body; my findings agree fundamentally with h4anteg a u z ' s description o f the effect of coca leaves: The first time I t o o k 0.05g. of cocai'num muriaricd:'.; ix 2 190water solution was when I was feeling 5l:ghiiY O'JI of sons from fatigue. This solution is rather viscous, somewhat opalescent, and has a suange eromatic smell. A t first it has a bitter taste, which yields efterwards to a series of very p l w a n t aromatic flzvors. Dry cocaine salt h2s the same smell and taste,

One feels a certain fumness o n the lips a n d palate, follou*ed by a feeling of wannth in the s a m e areas; if one now drinks cold water, it feels warm o n the lips a n d cold in the throat. On other occasions the predominant feeling is a rather pleasant coolness in t h e mouth and throat.
I

V
* .4 d A nis:cr e$ in subcutancour injecrion. ' LiLr Xschcnbrandt (Druischr mcd. H'ochcnschrijr,

Dcc.. 1SS3) I

uIcd :he hydro:hlo:ic p:cparation

[!IC]

of c o u i n c as described by Merk

ir Dcmsiadt. This preparation mry be bought in \'ienna in Haubner'r Engelapthekc am Hof ai a price which is not much higher t h r n Slc:k's [si:], but uhich must. neucrthclcrs. be rcgardtd ZI \ e > h i ~ h The management of rhc pharmrq in quu:ion is try. i 7 g . 2s ih:? ha\c bzcn Lind enough to inform me. io lou.cr the F X C of :he drus b> establishing neu sources of supply.

During this first trial 1 C.\pCriCnCed 3 s!iOrt period of io,\ic effects, u.hich did not rccur in subsequent expcrimenls. Brcaihing became slo\\cr and decpcr and 1 felt iired and sleepy; I ya\\.ned ficqucntly and fclr some\vhat dull. After a fcw minutes t h e aclual cocaine euphoria began, introduced by rcpearcd cooling erucration. Immediately a f i t r tzLing the coiainc ] noiiced a slight slackenins of Ihe pulse 2nd 1a;er a moderate increase. I ha\.e obscr\.ed rhe szme ph!.ciczl si_cns of ihe e f fect of cocaine in others, mostly p-oplc of my o\\n age. The mosr constant s!'np:on p:o\.ed I O be t h e :eptzred cooling eruclarion. This often i X @ m p z n i c d by a rumbling \vhich must originate from h i g h .up in the intes!ine; t\vo of the peosle 1 observed. \\!IO srid ;hey \Yere able to reco_c2iz: mc\cmenis of t h e i r stomachs, declared emphziiczily : h a t they hzd repeatedly detected such mc\emen:s. Oficn. .it the outset of the cocaine effeci, the subjects z!leged that they cspcricnced a n inter.se feeling cf h : in the head. I noriced this in myseif 2s \\e!] i n 15: :curse of >@me a i t r crpcrimenrs. b!~ron cther o c c 2 c i c i l s ii \\zs l absent. In only t w o cases did COG git,e rice I O diuiness. O n the whole the toxic effects of coca are of short duration, a n d much less intense thzn those produced by effeclive doses of quinine or salicy1r;c of soda, they seem to become even wezkei zfter reptated use of cocaine. h f a n i e g a u a refers IO t h e follou.ir!g o c t z : i c x ! effects of coca: iemporary cr)?hema, an increzse in rh: quantity o f urine, dryness of the conjuncri\ra and nasal mucous membranes. D c n e s s of the mucous membrane of the m o u t h and of the throat is a regular symptom which lzsts f o r hours. Some observers (Mamaud, Collan)'' report a slight czthanic effect. Urine and feces are said IO t2ke on rhc smell of coca. different accounts of Different o b s e n e r s give the effect o n the pulse rate. According t o Mznregaua, coca quickly produces a considerzbly increased pulse rate which becomes e\.en higher with hisher doses; Collin," too, nored 2n acceleration of the pulse after coca was taken, while Rossier," Demarle," and Manpaud experienced, after the initid acceleration, a longer lasting retardation of the pulse rate. Christison noticed in himself, after using coca, tht physical exertion caused a smaller incicase in i h t ~ulse rate than otherwise; Reiss" dispurcs a n y effect on the pulse rate. I do not find any difficulty in accounting for this lack of agreement; it is partly owing to the variety of the preparauons used (\\.arm infusion of the leaves, cold coczine solution. e t c . ) . and the way in which they are zpplied,' and pzrtly 1 0 the