,transcriber's ,notes ,obvious typographical errors have been silently corrected4 ,all other spelling and punctuation remains unchanged4 ,in particular the author uses ,kavahin for what is now normally referred to as ,kavain4 ,italics are represented thus italic4 ,,thesis presented for the degree of ,,master ,,of ,,science at ,,the ,,college ,,of ,,hawaii ,,june #aiae by ,,alice ,a4 ,,ball4 ,the ,thesis1 herewith1 on 8,the ,chemical ,constituents of the ,active ,principle of the ,ava ,root0 by ,alice ,a4 ,ball1 clearly demonstrates her ability to do original work and to present her results in logical form4 ,approved4 ,illustration3 ,j4 ,f4 ,illingworth ,chair of the ,committee on ,advanced ,degrees4 ,college of ,hawaii1 ,may #ad1 #aiae4 ,,the ,,chemical ,,constituents ,,of ,,piper ,,methysticum ,,or ,,the ,,chemical ,,constituents ,,of ,,the ,,active ,,principle ,,of ,,the ,,ava ,,root4 ,,index4 ,page #a4 ,historical #a #b4 ,method of ,extraction #g #c4 ,method of ,separation of the ,resins #i #d4 ,various ,metallic ,salts of the ,resinous ,acids #ab #e4 ,the ,total ,resins #ac #f4 ,the ,barium ,acid #ae #g4 ,oxidation ,products of the ,barium ,acids #ba #h4 ,the ,iron ,acids #bh #i4 ,oxidation of the ,iron ,acids and the ,free ,acids #cc #aj4 ,alcohol ,radicals #cd #aa4 ,methysticin and ,methysticinic ,acid #cf #ab4 ,physiological ,action #ch #ac4 ,conclusion #dc ,,historical4 8,among the customs peculiar to the inhabitants of the ,south ,pacific ,islands1 perhaps the most noted is that of the preparation and drinking of a narcotic beverage called ava1 kava1 or yakona4 ,much of its notoriety arises from the repulsive way in which it is sometimes made4 ,aside from this1 it is characteristic of a certain oceanic area1 and seems to be as strikingly limited to this area as is the stick-and-groove method of making fire4 ,the custom1 is not confined to one ethnic stock1 many notices in literature showing that both ,papuans and ,polynesians practise it4 ,in many of the islands the ,liquor is concocted by chewing the root of the ,macropiper methysticum1 or long pepper1 ejecting the comminuted mass into a bowl1 adding water1 straining out the pulp1 and drinking the fluid4 ,in other localities it is made by simply grating the root and adding water4 8,the plant from which kava is made is a shrub of the natural order ,piperaceae4 ,it is about six feet high with stems ranging from an inch to an inch and a half in thickness2 the leaves are cordate and from four to eight inches long4 ,this family is the source of the pepper of commerce and contains several species that are of medicinal and commercial importance4 ,in making kava1 the root and base of the stem is used4 ,the roots usually weigh from two to four pounds1 though sometimes as much as #bb pounds4 ,several varieties are distinguished by the natives2 for instance1 in ,tahiti there is a yellow variety called ,marea2 another1 which becomes pink on exposure to the air1 is called avini-ute4 8,chewed when freshly gathered1 the root first tastes sweet and aromatic1 then bitter1 acrid and pungent4 ,it provokes abundant secretion of saliva and in a few seconds occasions a sensation of burning on the tongue4 ,the root contains about fifty percent of starch1 a little pale-yellow essential oil1 two percent of an acrid resin1 and one percent of the neutral crystalline principle methysticin1 called kavahin4 ,to the latter principle we must attribute the toxic qualities of the kava preparation4 ,the resin and the kavahin are insoluble in water1 but are soluble in saliva and the gastric juices4 8,in ,samoa1 the ava root is grated or chewed1 then soaked1 the woody pulp strained off1 and the fluid drunk4 ,the root is used either dry or green4 ,the flavor of the liquid is at first like that of soapsuds1 but immediately afterward a pleasant aromatic taste is imparted1 faintly bitter1 as in quinine4 ,in ,samoa1 ava drinking is the accompaniment of all meetings of the men4 8,kava is at first stimulating1 but the effect of an excess resembles that of opium1 producing a drowsy drunkenness1 lasting for two hours4 ,the inebriate is usually peaceable1 but sometimes is irritated by noises1 which is attributed by natives to the use of kava grown in moist ground4 ,the results of excess are skin disease1 emaciation1 and general decrepitude4 ,the peculiar whiteness of the skin caused by kava drinking is said to be sought after in some islands as a sign that its possessor is wealthy enough to devote his time to its acquirement4 8,there is some misapprehension in regard to whether the liquid undergoes fermentation before it is consumed1 but it is positively known that there can be no fermentation1 for the liquor is drunk immediately after the addition of water to the macerated root4 ,kava that is prepared by chewing is said to be more palatable1 which is perhaps due to the conversion of the starch into a fermentable substance by the ptyalin of the saliva40#a #a--;,by ,walter ,hough--,reprinted from ,smithsonian ,miscellaneous ,collections--,no4 #adgb--;,august #aijd4 8,kava ,drinking as ,practised by the ,papuans and ,polynesians40 8,in #aggi ,captain ,king1 ,r4 ,n41 who followed ,captain ,cook to the ,islands1 describes the case of a priest as follows #8a little old man of an emaciated figure1 his eyes exceedingly sore and red1 and his body covered with a white leprous scurf1 the effects of an immoderate use of ava4' ,he also says1 #8,the chiefs suffer dreadful effects from the immoderate use of ava4 ,those who are most affected by it had their bodies covered with a white scurf1 their eyes red and inflamed1 their limbs emaciated1 their whole frame trembling and accompanied with a disability to raise the head4'0#b #b 8,leprosy ,prize ,essays10 #bnd series by ,thompson and ,cantile1 #ahig4 ,f4 ,a4 ,griel1 makes the following statement in a foot note4 8,the mixture is a subnarcotic1 and if drunk by ,european sailors produces highly nauseous effects4 ,if frequently taken a dry burning heat is produced all over the body1 the eyes become red1 skin peels off in flakes and then degenerates into leprous ulcers or the whole body becomes emaciated and wastes away40#c #c ,miquel1 ,systema ,piperacearum4 ,numerous attempts have been made to isolate the active chemical constituent or constituents4 ,as early as #ahdd ,morson discovered an active principal ,kawine4 ,this is a greenish-yellow1 strongly aromatic and acrid resin4 ,this was again studied by ,cuzant in #ahfj4 ,gobley isolated from kava root a crystalline principle 7analogous to piperin71 methysticin1 or kavahin1 which is without odor and taste and is probably inert4#d ,in #ahhf ,lewin separated the resin into two resins1 of which the ,beta resin is greasy and of a reddish-brown color1 appearing in mass almost black4 ,this is less active than the alpha resin which is yellowish brown1 has the characteristic odor of the drug1 is freely soluble in alcohol1 and placed upon the tongue produces a burning sensation followed by local anaesthesia4#e #d ,j4 ,p4 ,c4 ,jan4 #ahfj4 #e ,a4 ,j4 ,p4 #ahhf1 #dej4 ,a volatile oil has been found in the root4#f #f ,j4 ,p4 ,c4 ,march #ahfb4 ,lavialle claimed to have obtained an alkaloid1 ,kavaine4#g #g ,l',union ,pharm4 ,jan4 #ahhi4 ,the following statement was found in 8,watts ,chemical ,dictionary01 8,kawain--a crystalline resin occurring along with methysticin in kawa-kawa1 ,it is not a glucoside4 ,on oxidation it yields benzoic acid4#h #h ,gobley1 ,j4 ,ph4 7#c7 #cg1 #ai4 ,the following statement appears in the ,encyclopedia ,britannica4 8,there appears to be little doubt that the active principle in this beverage is a poison of an alkaloidal nature4 ,it seems likely that this substance is not present as such 7i4e4 as a free alkaloid7 in the plant1 but that it exists in the form of a glucoside1 and that by the process of chewing1 this glucoside is split up by one of the ferments in the saliva and the free alkaloid and sugar is formed04 ,arthur ,bossingham#i communicates the results of a chemical examination of ,kava-kava4 ,besides the crystalline body1 methysticin1 which has already been described by others1 he was able to isolate and identify three resins1 one soluble in #e solution of potassium carbonate1 the second insoluble in this1 but soluble in #e solution of caustic potash1 while the third was insoluble in both of these alkaline solvents1 ,the ash amounts to #b4die of the air dried root1 and contained besides mere traces of ,fe1 ,mn1 mainly ,calcium1 ,sodium and ,potassium4#aj #i ,proc4 ,a4 ,ph4 ,a4 #ahih1 #efd4 #aj ,proc4 ,wisc4 ,pharm4 ,assos4 #ahih1 #ec1 #ee4 ,,method ,,of ,,extraction4 ,the fresh rhizome was chopped up and then ground up by means of a meat chopper4 ,in the preliminary work the material was dried in a vacuum oven at a temperature not exceeding forty degrees ,centigrade4 ,in the later work the material was rapidly dried in the sun4 ,this operation required about two days time4 ,after being thoroughly dried1 the material was finely powdered1 and then extracted with ether4 ,the following continuous extraction apparatus was used4 ,due to the extreme rapidity with which the ether evaporated1 it was necessary to surround the coils with ice so as to keep the condensers cold4 ,illustration3 ,diagram of apparatus ,,method ,,of ,,separation ,,of ,,the ,,resins4 ,after the removal of the crystalline methysticin from the extract1 the following method of separation of the resinous products was used4 ,the free acids were removed by shaking the total resins successively with solutions of one percent ammonium carbonate1 one percent sodium carbonate and one percent sodium hydroxide4 ,the acids thus removed were recovered by treating the alkaline solution with dilute hydrochloric acid and shaking out with ether4 ,the three acids were not markedly different in their physical properties4 ,they possessed the characteristic odor of the crude drug1 were viscous1 brown in color and did not solidify at minus ten degrees ,centigrade4 ,these free acids constitute about five percent of the total resins4 ,the remainder of the extract was treated with alcoholic potassium hydroxide and saponified by heating the solution to about eighty degrees for fifteen minutes4 ,after the alcohol was removed by distillation a small quantity of water was added4 ,this resulting solution was then extracted with ether to remove the alcohol radical or radicals and the unsaponifiable material from the saponified product4 ,the ether extract was saved to be used in the work on the alcohol radicals4 ,the aqueous portion was evaporated to a semi-solid mass4 ,carbon dioxide was passed over this mass for about fifteen minutes to change any excess of potassium hydroxide to potassium carbonate4 ,alcohol 7#ie7 was then added to precipitate the carbonate4 ,the carbonate was then filtered off and water added to the filtrate4 ,to the clear filtrate a solution of barium chloride was added4 ,immediately a dense thick cream yellow precipitate formed4 ,barium chloride was added in excess4 ,the barium salt was filtered off by means of a suction pump and the precipitate washed with water4 ,the filtrate was treated with a few drops more of barium chloride so as to be sure that an excess had been added1 which was proven if no further precipitate formed4 ,to this clear filtrate an excess of a solution of ferric chloride was added4 ,immediately a thick heavy precipitate of the iron salt came down1 which was filtered off by means of a suction pump and the precipitate washed with water4 ,the barium precipitate was treated with dilute hydrochloric acid and heated to boiling to decompose the barium resinate1 and to liberate the free resin acid4 ,the liberated acid was a brown resin of a thin consistency and had a characteristic odor4 ,this acid was removed by shaking out with ether4 ,the ethereal solution was dried with anhydrous sodium sulphate1 filtered1 and the ether removed by distillation4 ,the last traces of ether were removed by heating the resin acids in a vacuum oven at sixty five degrees ,centigrade4 ,this resinous acid is the acid spoken hereafter in this paper as the ,,barium ,,acid4 ,the iron precipitate was treated with dilute sulphuric acid 7ferric chloride is soluble in ether and ferric sulphate is not7 and heated to boiling to decompose the iron resinate4 ,the acid when liberated had a strong characteristic aromatic odor4 ,it was extracted with ether in the same manner as the barium acid4 ,this resinous acid is the acid spoken of in this paper as the ,,iron ,,acid4 ,the resinous extract left after the removal of the crystalline methysticin is spoken of as the ,,total ,,resins4 ,the resin acids removed by the preliminary shaking out with the various aqueous alkalies are spoken of as the ,,total ,,free ,,acids4 ,,the ,,various ,,metallic ,,salts ,,of ,,the ,,resinous ,,acids4 ,after obtaining the potassium salts of the acids and having freed the same from the excess of the potassium hydroxide and potassium carbonate1 the possibilities of the formation of different metallic salts were tried4 ,the soluble salts of the following metals yielded precipitates3-- ,manganese ,barium ,cobalt ,silver ,mercury ,iron ,zinc ,copper ,calcium ,lead ,the following metallic salts gave a complete precipitation3-- ,silver ,iron 7ferric7 ,manganese ,since the barium and iron 7ferric7 salts gave the best means of separation1 they were used to separate the resins4 ,,the ,,total ,,resins4 ,the total resins were brown in color1 thick syrupy consistency and possessed the characteristic odor of the drug4 ,a molecular weight determination was made in the same manner as with the ,barium acids1 and the following data obtained4 ,wt4 of pipette before #ah4gffj ,wt4 of pipette after #ad4gafj ,wt4 of resin used #d4jejj ,temperature before #c4eb ,temperature after #c4ga ,change in temperature 4#ah ,volume #cg cc4 ,constant for solvent #cbhj ,approximate molecular weight #bjjj ,combustions were made and the following data obtained4 ,wt4 of boat #c4dgbb #c4dgbj ,wt4 of boat and resin #c4fcee #c4fbbj ,wt4 of resin 4#afcc 4#aejj ,sulphuric acid tube #gi4ajea #gi4chfe ,tube plus water #gi4bjgc #gi4dggj ,water 4#ajbb 4#jije ,hydrogen equivalent 4#jaacf 4#jajjf ,,koh bulb #di4dcaf #ej4hgbj ,bulb plus carbon dioxide #di4hcej #ea4bdcj ,carbon dioxide 4#djcd 4#cgaj ,carbon equivalent 4#abajb 4#ajaj ,percent ,carbon #fg4ca #fg4c ,percent ,hydrogen #f4i #f4g ,percent ,oxygen #bf4h #bg4j ,the total resins when placed on the end of the tongue produced a marked stinging sensation followed by a local anaesthesia4 ,after the first stinging was produced the sensation was rather pleasant4 ,the local anaesthesia persisted a long time1 giving a sensation much the same as that produced by cocaine4 ,the barium and iron acids also produced this local anaesthesia1 but the initial stinging sensation was much more pronounced1 which was probably due to the acid nature of the substance4 ,,the ,,barium ,,acid4 ,the resinous material used and spoken of as the 8,barium ,acid0 is the material prepared and so named as given under the 8,method of ,separation04 ,,physical ,,properties3--,dark reddish brown in color1 syrupy in consistency and has a characteristic odor2 heavier than water2 soluble in benzol1 ether1 alcohol and acetone1 but insoluble in petroleum ether and water4 ,this resin constitutes about sixty percent of the total ester resins2 i4e4 the resins left after the free acids have been removed with aqueous potassium hydroxide4 ,an analysis of the barium salt obtained by precipitation from the potassium soap was made and the following data obtained3-- ,wt4 of substance used #a4agae 4#ehfj ,wt4 of barium sulphate 4#ddcj 4#bbje ,barium equivalent 4#bfjf 4#abih ,percent barium #bb4b #bb4a ,the following method was used in making the above analysis4 ,the weighed material was ignited in a platinum crucible by gently heating until the combustible gases formed were given off4 ,the crucible was then more strongly heated to completely burn off the carbonaceous material left4 ,the residue was extracted with nitric acid and the barium precipitated as the sulphate with dilute sulphuric acid1 and the weight of the barium sulphate determined4 ,expressed as the ,,acid ,,number1 or the number of milligrams of potassium hydroxide required to neutralize the free acids in one gram of the substance1 the following data was obtained3-- ,barium equivalent 4#bfjf 4#abih ,barium expressed as ,,koh equiv4 4#baca 4#ajfb ,wt4 of material used #a4agae 4#ehfj ,milligrams of ,,koh per gram #aha4i #aha4c ,,acid ,,number #aha4i #aha4c ,the following gives the ,,acid ,,number obtained by direct titration of the barium acid2 in 8,a01 barium hydroxide was used and in 8,b01 sodium hydroxide was used4 ,a small quantity of the material was dissolved in a sufficient quantity of neutralized alcohol to give a liquid of a light yellow color1 ,phenolphthalein was used as the indicator1 and the alkali was added until a red color was produced4 8,a0 8,b0 ,wt4 of substance 4#fafj 4#bcde ,cc4 of alkalie #d4ed #a4ge ,,koh equiv4 per gram #da4dj #da4ij ,acid number #da4dj #da4ij ,on evaporating a portion of the alcohol from the material left after titrating with the sodium hydroxide1 and adding water to obtain an aqueous solution of the sodium salt1 an emulsion was formed1 and on standing globules of the free resinous acid separated4 ,from the data thus obtained1 it can readily be seen that the acid or acids which constitute the ,,barium ,,acid must have a number of carboxyl groups and form a different series of salts by precipitation than by direct titration4 ,the salt or salts formed by direct titration1 although neutral to phenolthalein may be acid in structure4 ,this is further shown by the fact that the potassium salts produced by direct titration are readily hydrolyzed4 ,the acid number obtained by the precipitation of the barium salt may be called the ,,combining ,,value1 and the acid number obtained by titration the ,,titration ,,value4 ,a number of molecular weight determinations were made on the free barium acid4 ,mc,coy's ,boiling ,point ,apparatus was used and ,merk's benzol 7free from thiophene7 was used as the solvent4 ,a weighing pipette with a bulb was used to introduce the material1 the bulb being weighed before the material was introduced into the apparatus1 and afterwards1 the difference being the weight of the material used4 ,wt4 of pipette 7before7 #af4cfgj #ad4hhie ,wt4 of pipette 7after7 #ad4hhie #ab4dfaj ,wt4 of material used #a4ebbe #b4dbhe ,original temperature #c4ec #c4ec ,final temperature #c4fj #c4fb-c ,change in temperature 4#jg 4#ji ,volume of solution #cg cc #dc4e cc ,constant for solvent #cbhj #cbhj ,approx4 ,molecular ,wt4 #bjjj #bajj or #ahjj ,combustions were made using the barium acids4 ,by qualitative tests it was found that the acids contained only carbon1 hydrogen and oxygen4 ,the following gives the results of the combustions4 ,wt4 of boat #b4hdjb #b4hdjb ,wt4 of boat and resin #c4jejj #c4jbej ,wt4 of resin 4#bjih 4#ahdh ,wt4 of ,h#b,,so#d tube #gh4jbej #gh4adae ,wt4 of tube plus water #gh4aebj #gh4beej ,wt4 of water 4#abgj 4#aace ,hydrogen equiv4 4#jadc 4#jabf ,wt4 of ,,koh bulb #dh4hadj #ea4gjie ,wt4 of bulb plus ,,co#b #di4chjj #eb4bjhe ,wt4 of ,,co#b 4#effj 4#diij ,carbon equiv4 4#aedc 4#acfa ,percent ,hydrogen #gh4e #gc4f ,percent ,carbon #f4h #f4h ,percent ,oxygen #ai4g #ai4f ,an attempt was made to make the potassium salts of the barium acids by saponification with alcoholic potash4 ,a small quantity of the acid was treated with an excess of ten percent alcoholic potash and heated to eighty degrees ,centigrade to complete the saponification4 ,instead of the formation of the potassium salts1 a thick dark brown solid1 gummy mass separated4 ,on cooling it solidified to a brittle solid which had all the physical properties of a true resin4 ,this solid is soluble in ether1 chloroform and benzol1 slightly soluble in alcohol and insoluble in petroleum ether and water4 ,it burns without the formation of an ash4 ,evidently1 this brittle material is a condensation product of the original barium acid4 ,,oxidation ,,products ,,of ,,the ,,barium ,,acids4 ,a small amount of the ,barium acids was sealed with concentrated nitric acid in a hard glass tube and heated in a bomb furnace for an hour and a half at #aae to #abj degrees ,centigrade4 ,on cooling a yellow solid separated4 ,qualitative tests showed that this oxidation product contained no nitrogen1 combined with sodium hydroxide readily1 is soluble in hot water1 slightly soluble in cold water1 easily soluble in ether1 alcohol and benzol and slightly soluble in carbon tetrachloride4 ,it decolorizes alkaline permanganate but does not decolorize bromine water4 ,that there are a number of intermediate products formed and that nitration also takes place during the formation of these intermediate products is shown by the following4 ,a small quantity of the acids were placed in a test tube and covered with concentrated nitric acid4 ,this was suspended in an ,h#b,,so#d bath and a thermometer inserted so as to observe the temperature4 ,on being gently warmed the nitric acid and the resin began to react with a rapid evolution of carbon dioxide and oxides of nitrogen4 ,as soon as the reaction had modified and before the temperature rose above one hundred degrees ,centigrade1 a small amount was removed and added to water4 ,some of the solid acid was formed and also a number of globules of oil and there was a strong persistent odor of nitrobenzene4 ,the original test tube was heated to about one hundred and twenty degrees centigrade and a small portion again removed4 ,there was more of the solid material formed and the odor was similar to vanillin or coumarin or cinnamic aldehyde4 ,the test tube was again tested when the temperature had reached one hundred and thirty five degrees ,centigrade4 ,there was no aromatic odor and a large amount of the solid formed4 ,when viewed under the microscope the substance had the appearance of curled threads4 ,when the barium acids were treated with the standard nitrating mixture1 a solid was obtained which showed the presence of nitrogen when the standard test was applied4 ,after the preliminary tests were made1 the following method of preparation was used4 ,two or three grams of the barium acids were introduced into a hard glass tube of about thirty centimeters in length and fifteen or twenty cubic centimeters of concentrated nitric acid added4 ,the reaction which is very vigorous at first was regulated by keeping the tube under running water4 ,after this vigorous action was over the tube was placed in a sulphuric acid bath1 and the temperature gradually increased until it had reached one hundred and twenty five degrees ,centigrade1 at which temperature it was kept for about five hours4 ,it was necessary to add a small quantities of nitric acid from time to time to make up the loss by evaporation4 ,when the oxidation was completed the product was poured into water and then heated to boiling4 ,the resulting solution was filtered and the filtrate allowed to cool4 ,on standing a quantity of a pale yellow substance separated4 ,the following data gives the percent yield of this oxidation product4 ,wt4 of container #f4gbbj ,wt4 of container and substance #g4eibj ,wt4 of substance 4#hgjj ,wt4 of oxidation product 4#abdj ,percent yield #ad ,the oxidation product was dried by placing it in a vacuum over sulphuric acid for several days4 ,the neutralization equivalent of this crude oxidation product was #aeg4 ,wt4 of substance used 4#jejb ,number ,cc4 of ,na,o,h ,n_/#aj #c4b cc4 ,neutralization equivalent #aeg ,the oxidation product was heated on a watch crystal and the sublimate allowed to collect on a funnel4 ,the first sublimate gave a melting point of #aji degrees ,centigrade4 ,combustions were made on this sublimate with the following results4 7#a7 ,c #ff ,h #d4g 7#b7 ,c #fe4g ,h #d4h 7#c7 ,c #fe4ae ,h #d4h 7#d7 ,c #fe4h ,h #d4he ,the neutralization equivalent was obtained by titrating an alcoholic solution of the sublimate with standard sodium hydroxide4 ,the following results were obtained on two different lots of the sublimed oxidation product4 ,wt4 of substance 4#ji 4#ajjf ,cc4 of alkali ,n_/#aj #g cc #g4i;cc ,neutralization equiv4 #abh4f #abg4c ,using a third sample the neutralization equivalent was obtained from the analysis of the silver salt4 ,the silver salt was formed by adding silver nitrate solution to a carefully neutralized solution of the sublimate4 ,the insoluble silver salt was filtered off1 washed with water to remove the excess of silver nitrate1 and dried in a vacuum over sulphuric acid for several days4 ,a weighed quantity of the silver salt was ignited in a platinum crucible and the residue of metallic silver was weighed4 ,the following data were obtained using material from the same sample for each analysis4 ,wt4 of dish #ab4hhbe #ab4hhbf ,wt4 of dish and substance #ac4jjfj #ac4acaj ,wt4 of substance 4#abce 4#bdhd ,wt4 of dish and silver #ab4idjj #ab4iihj ,wt4 of silver 4#jege 4#aaed ,neutralization equiv4 #abe #abe4c ,using the same sample1 a neutralization equivalent was obtained by titration with standard ,na,o,h4 ,wt4 of substance 4#jiab ,n_/#aj ,na,o,h #g4be;cc ,neutralization equiv4 #abe4h ,the above data shows that the sublimate is a mixture4 ,no empirical formula can be calculated from the combustions1 and different samples give different neutralization equivalents although the duplicate determinations on the same sample showed good agreement thus demonstrating the reliability of the methods4 ,by fractional sublimation it was possible to obtain fractions with different melting points4 ,the first sublimate melted sharply at #aji degrees4 ,from the last fraction it was possible to separate some crystals that melt at #bjj degrees ,centigrade4 ,these might possibly be p-acetyl-benzoic acid1 as its properties of solubility1 crystalline form1 its melting point and power of sublimation agree with those of p-acetyl-benzoic acid4 ,those crystals that appeared identical with benzoic acid were placed in a melting point tube1 and some known benzoic acid 7from toluol7 was placed in another tube4 ,these two tubes were placed in the same sulphuric acid container and their melting points taken at the same time4 ,they melted at the same temperature4 ,the sublimate had a very pleasant aromatic odor resembling benzoin4 ,it gave no coloration with ferric chloride1 thus eliminating a large group of aromatic compounds4 ,some of the crystals were found to be identical with benzoic acid when examined under the microscope4 ,the characteristic odor of methyl benzoate was produced when a small quantity of the crystals were heated with methyl alcohol and concentrated sulphuric acid4 ,on treating some of the carefully neutralized product with ferric chloride solution1 a flesh colored precipitate was formed4 ,it agreed closely in its analysis with the precipitate formed with known benzoic acid4 ,the filtrate left after the removal of the iron precipitate was acidified and extracted with ether1 and the ether removed by evaporation4 ,the resulting substance decolorized alkaline permanganate solution1 but did not decolorize bromine water4 ,when the leaflet needles that melt at #bjj degrees were mechanically removed from the original sublimate1 the substance left after precipitating with ferric chloride melted at #aji degrees4 ,when these crystals were not removed1 the melting point of this material was not definite1 but was over a range of five degrees1 from #aaj to #aae degrees ,centigrade4 ,the oxidation product contains at least three distinct substances1 benzoic acid1 a substance melting at #bjj degrees and--which is probably p-acetyl benzoic acid and a third substance melting at #aaj degrees4 ,,the ,,iron ,,acids4 ,the resinous material used and spoken of as the ,,iron ,,acids is the material prepared and so named under the 8,method of ,separation04 ,,physical ,,properties3--,transparent and reddish brown in color1 oily in consistency and has a characteristic tea like odor1 heavier than water1 freely soluble in benzol1 ether1 alcohol and acetone1 but insoluble in petroleum ether and water4 ,this resin constitutes about eighteen percent of the total ester resins4 ,by qualitative tests it was shown that the acids contained only carbon1 hydrogen and oxygen4 ,combustions made on the iron acids gave the following results4 ,wt4 of boat #b4fiej #b4fiej ,wt4 of boat and substance #b4hdgj #b4hdie ,wt4 of substance 4#aebj 4#aede ,,koh bulb #ej4ifbj #ea4jhje ,bulb and ,,co#b #ea4ccgj #ea4dfaj ,wt4 of ,,co#b 4#cgej 4#chje ,carbon equivalent 4#ajbc 4#ajcgf ,sulphuric acid tube #gf4bddh #gf4cdej ,tube and water #gf4cdjj #gf4ddec ,wt4 of water 4#jieb 4#ajjc ,hydrogen equiv4 4#jajf 4#jaaad ,percent ,carbon #fg4c #fg4b ,percent hydrogen #g4j #g4b ,percent ,oxygen #be4g #be4f ,an analysis of the iron salt obtained by precipitation from the potassium soap gave the following data4 ,wt4 of substance used 4#biee 4#cchg ,wt4 of ,fe,s,o#d 4#jdde 4#jeji ,ferric equiv4 4#jcbjh 4#jcfgf ,percent ,iron #aj4he #aj4he ,the following method was used in making the above analysis4 ,the weighed material was ignited in a platinum crucible by gently heating until the combustible gases formed were given off4 ,the crucible was then strongly heated until the carbonaceous material was completely burned off4 ,the residue was weighed and the percentage of iron determined4 ,expressed as the ,,acid ,,number1 or the number of milligrams of ,,koh required to neutralize the free acids in one gram of the substance1 the following data was obtained4 ,ferric equivalent 4#jcbjh 4#jcfgf ,fe expressed as ,,koh equiv4 4#jife 4#aajg ,wt4 of material used 4#biee 4#cchg ,mg4 of ,,koh per gram #cbf4f #cbf4g ,acid number #cbf4f #cbf4g ,the following gives the ,,acid ,,number obtained by direct titration of the ,iron acid4 ,the method is the same as that used in getting the titration value of the ,barium acid4 ,wt4 of substance 4#bdej 4#bdgb ,cc of alkalie #b4b #b4c ,,koh equiv4 4#jabcb 4#jabhh ,,koh equiv4 per gram #ec4hg #eb4 ,an attempt was made to saponify some of the iron acid1 but it was impossible4 ,the alcohol was partially distilled off1 and the acid freed by making the mass acid with sulphuric acid1 and shaking out with ether4 ,the ether was distilled off1 but the remaining acid had different physical properties from the acid with which the experiment was started4 ,it was lighter in color1 and solidified at zero degrees4 ,at room temperature it was almost solid4 ,on ignition it left no ash4 ,this probably is a polymerization product of the original acid4 ,since many organic acids whose salts cannot be prepared by the ordinary methods can be prepared by passing dry ammonia gas through a solution of the acid in anhydrous ether1 this method was tried with the iron acid4 ,the iron acid was dissolved in anhydrous ether1 and the dry ammonia gas was bubbled through this ether solution4 ,at first no change was noted1 but after several minutes there was a flocculent thready precipitate formed which was light brown in color4 ,the experiment was repeated4 ,at first the precipitate was a very light brown1 but after forming it quickly darkened4 ,after standing a few hours the flocculent precipitate changed to a sticky brown mass4 ,this same change was produced immediately if the precipitate was exposed to the air4 ,the resulting mass had no odor of ammonia4 ,the flocculent precipitate formed at first was probably the ammonium salt of the iron acid1 which like most ammonium salts1 it was precipitated due to its insolubility in ether4 ,due to the ease of hydrolysis this salt immediately decomposed to the acid and ammonia when traces of moisture were present4 ,,oxidation ,,of ,,the ,,iron ,,acids ,,and ,,the ,,free ,,acids4 ,when the iron acids were oxidized in the same manner as the barium acids the amount of the oxidation product formed was about one fourth of that produced with an equal amount of the barium acids4 ,the time necessary to completely oxidize the iron acids was much less then required for the barium acids4 ,on sublimation the iron acid gave a product melting at #aaj degrees ,centigrade and is probably identical with the one formed from the barium acids4 ,the iron acid also yielded a sublimate melting at #bjh degrees ,c4 ,the free acids when oxidized in a like manner gave as one of the products a low melting crystalline compound that contained nitrogen4 ,the iron acid although related to the barium acid as shown by the formation of a common oxidation product is different in structure as shown by the difference in the amount of the oxidation product formed and the time to complete the oxidation4 ,,the ,,alcohol ,,radicals ,,and ,,unsaponifiable ,,material4 ,the material that was shaken out with ether after the saponification consists of the unsaponifiable material and the alcohol radicals of the acids produced by saponification4 ,on allowing the ether to evaporate from this material1 feathery needles separated4 ,these were removed by means of a suction pump and recrystallized from hot acetone4 ,the melting point of this product was #abb-abe degrees ,centigrade4 ,the precipitate was dissolved in benzol and allowed to slowly crystallize4 ,it formed long prismatic needles with melting point of #acj degrees ,centigrade4 ,when heated with concentrated sulphuric acid1 a brown green fluorescent solution was produced4 ,the remaining material was steam distilled1 and the distillate extracted with ether to remove the oil4 ,the ether was dried with anhydrous sodium carbonate1 the solution filtered and the ether removed by distillation4 ,the oil that remained was light yellow1 specific gravity less than that of water1 and possessed a very characteristic odor resembling that of musk4 ,the material left after the steam distillation was cooled and shaken out with ether4 ,the ethereal solution was dried with anhydrous sodium sulphate and the ether removed by distillation4 ,the resulting mass was a dark brown resin without any characteristic odor1 solidifying at zero degrees4 ,the crystalline product with a melting point of #acj degrees and the essential oil are evidently the alcohols formed through saponification of the resin esters4 ,the crystalline product could be readily separated from the resinous material because of its slight solubility in acetone4 ,since this product was not precipitated when the unsaponified resin esters were treated with acetone and because it did not make its appearance until after the process of saponification1 it is quite probable it is a product of saponification4 ,the essential oil can be detected in extremely small amounts due to its penetrating characteristic odor4 ,before the process of saponification it could not be detected1 but as soon as saponification took place the odor was very marked4 ,from this it is quite evident that this oil is a product of saponification4 ,the dark brown resinous mass that remained may be either an alcoholic resin formed through the hydrolysis of the ester resins or it may be a resin belonging to the class known as resenes#aa which resist saponification4 #aa ,com4 ,organic ,analysis4 ,allen ,vol4 ,,ii1 #adf4 ,,methysticin ,,and ,,methysticinic ,,acid4 ,the crystalline product obtained from the ether extract was recrystallized several times from absolute alcohol to remove all traces of any resinous material4 ,it had a melting point of #abb-abc4 ,it therefore was not pure methysticin1 which has a melting point of #ach-aci degrees4 ,on examining this product under the microscope it was found to contain two distinct forms of crystals1 long needles and prismatic plates4 ,some free methysticinic acid1 melting point #ahj was examined under the microscope and found to consist entirely of prismatic plates4 ,therefore the original crystalline body contains some methysticinic acid4 ,some of the original precipitate was crystallized once from absolute alcohol and thoroughly dried4 ,this was used for the following data to determine the percent of free methysticinic acid in the crystalline product4 ,a weighed amount of the crystalline product was dissolved in carefully neutralized alcohol1 and titrated with tenth normal ,na,o,h1 using phenolthalein as the indicator4 ,wt4 of substance used 4#beij ,na,o,h ,n_/#aj 4#e cc methysticinic acid4 ,the potassium salts of the various resin acids formed by the saponification of the ester resins should yield a resinous mass syrupy or oily in consistency when acidified1 if it consists entirely of the two groups of acids spoken of as the iron acids and the barium acids4 ,also the weight of the barium acids plus the weight of the iron acids should nearly equal the weight of the ester resins1 if these are the only two acids1 because the alcohol radicals constitute not more than two percent of the ester resins4 ,but when the total potassium salts were acidified the product formed contained a crystalline substance in addition to the resinous acids4 ,this crystalline substance was separated from the resinous acids by means of their difference in solubility in ether4 ,on recrystallization from absolute alcohol1 it had a melting point of #agi degrees ,centigrade4 ,it is therefore methysticinic acid4 ,this acid constitutes about twenty percent of the total acids from the ester resins because the barium and iron acids constitute only about seventy five percent4 ,this methysticinic acid cannot be entirely formed by hydrolysis of methysticin which was incompletely removed from the resinous material4 ,the methysticinic acid existed either combined with some other alcohol than methyl alcohol or was combined with one of the resin alcohol radicals4 ,,physiological ,,action4 ,due to the impossibility of preparing the alkali salts of the barium and iron acids so as to be positive that the resulting preparations completely represented the barium and iron acids1 and due to the insolubility of the acids and the total resins in solvents from which they would not again be precipitated when introduced into the circulation1 it was found necessary to make an emulsion4 ,the emulsifying agent used was acacia 7gum arabic74 ,it was possible by careful preparation to make a permanent emulsion that was miscible with water in all proportions to form a homogeneous mixture4 ,the animals used were rabbits of about six pounds weight4 ,the injections were made by ,dr4 ,geo4 ,mc,coy1 director of the ,leprosy ,investigation ,station at ,kalihi4 ,all the physiological experiments were made at the bacteriological laboratory at the ,leprosy ,investigation ,station4 ,one cubic centimeter of the emulsion of the total resinous extract 7strength #a in #e7 was injected into the ear of a rabbit2 the animal died immediately4 ,another rabbit was injected in the same manner with one half cubic centimeter of the same preparation4 ,the animal immediately stretched out and became rigid1 or appeared to be paralyzed1 but after several minutes these symptoms lessened and after about five minutes the rabbit appeared normal as far as activity was concerned4 ,as soon as the rabbit had recovered a second injection of one quarter of a cubic centimeter of the same preparation was injected in the same manner into the same animal4 ,the same symptoms were produced and with equal intensity1 but ten minutes passed before the animal again became conscious4 ,for several minutes after recovery the animal appeared somewhat drowsy and stupid but it soon regained its former activity4 ,one half cubic centimeter of the iron acid emulsion 7strength #a in #g7 was injected into the ear of a rabbit4 ,immediate paralysis and apparent anaesthesia set in lasting very pronouncedly for eight minutes4 ,the rabbit's head was drawn backwards and its legs stiffened giving symptoms similar to strychnine poisoning but they did not persist4 ,when a second injection of one quarter cubic centimeter was given to the same animal1 the same symptoms were produced1 the animal remaining under the influence of the injection for about fifteen minutes4 ,the iron acid injection was repeated on another rabbit with the same pronounced symptoms of strychnine poisoning but the effect lasted only about ten minutes4 ,one half cubic centimeter of the barium acid emulsion 7strength #a in #g7 was injected into the ear vein of a rabbit4 ,the animal uttered several loud cries and after moving several feet it became spastic and went into a sort of a stupor1 beginning to come out of it after ten minutes4 ,as soon as the animal recovered1 a second injection of one quarter cubic centimeter was made4 ,the animal again uttered loud cries and then it went into a stupor1 but it was not spastic4 ,this lasted approximately ten minutes4 ,the animal did not completely recover until about twenty minutes4 ,thinking that the action might be largely mechanical and that the symptoms produced were from the emulsion itself and not from the effect of the material that was emulsified1 an emulsion of olive oil was used in a like manner4 ,this olive oil emulsion was made in approximately the same consistency as the resinous emulsions1 and one cubic centimeter was injected into the ear vein of a rabbit4 ,no visible effects followed this injection during the one hour's time the rabbit was under observation4 ,one cubic centimeter intraperitoneal injections of the total resinous extract emulsion and the same amount of the iron acid emulsion were made into rabbits4 ,during the three hours the animals were under observation no symptoms were produced4 ,this may have been due to the extreme slowness of absorption as compared with the rate of elimination from the circulation4 ,dr4 ,j4 ,f4 ,illingworth states as the result of his observations while in the ,fiji ,islands that the kava beverage even when taken in large amounts1 does not apparently affect the brain to an extent as to cause the drinker to appear as if under the influence of alcohol1 but he appears as if the muscles from the hips downward are paralyzed4 ,these symptoms last for about half an hour1 at the end of which time the person is perfectly able to walk home4 ,in general the active constituent of any drug produces a more pronounced but more fugitive effect than the crude drug itself1 and one might therefore expect more violent reactions from the isolated active constituents of the ,ava then from the crude infusion4 ,judging from the negative results obtained from the injection of the olive oil emulsion1 it is probable that the physiological effects described above following the intravenous injections of the various preparations were not mechanical but must be ascribed to the action of the constituents of the ,ava4 ,,conclusion4 ,the crystalline product consists1 largely of methysticin1 the methyl ester of methysticinic acid4 ,in addition to this there is about five percent of the free methysticinic acid present4 ,the resinous product consists of about five percent of free resinous acids1 which acids can be separated into three different acids or groups of acids according to their solubility in the different alkalies4 ,the remaining resinous product is composed of ester resins4 ,on hydrolysis these esters yield three distinct acids1 two resinous acids and methysticinic acid4 ,the two resinous acids are distinctly different1 both in physical properties and in chemical properties4 ,they can be sharply separated by means of the difference in solubility of their barium and iron salts4 ,these acids may be separate individual substances1 or a group of related substances4 ,the barium and iron acids although different chemically1 have some groups in common as shown by the formation of a common oxidation product4 ,there are at least three alcohol radicals formed through hydrolysis1 a resinous alcohol radical1 a crystalline substance with a melting point of #acj degrees1 and a volatile oil4 ,the physiological action of the ,ava is due to the ester resins4 ,the two resinous acids formed through the hydrolysis of these esters seem to be the two active constituents of the resin ester4 ,from the above outlined work it appears that the ava root does not contain any alkaloidal substance1 as none of the constituents were found to contain nitrogen4 ,that the aqueous infusion used by the ava drinkers contains the same constituents as are extracted by the ether is shown by the following4 ,an infusion of the ava was made by allowing some of the powdered drug to remain in contact with water for about twelve hours4 ,the infusion was then filtered and the filtrate extracted with ether4 ,a resinous mass remained which from all appearances was identical with the resins obtained from the ether extract4 ,it also gave the same action when placed on the tongue as was produced by the resins from the ether extract4