Doc 0000151808

The page displays a stylized graphic of a bank vault door on the left, with text on the right. The text states that the document was obtained from an online database called "The Black Vault," which houses declassified government documents. Specifically, it mentions that this record is part of the MKULTRA/Mind Control Collection, containing over 20,000 pages declassified by the CIA. A website address, "http://mkultra.theblackvault.com," is provided for downloading the entire collection. There are no photographs, handwritten annotations, official stamps, forms, diagrams, tables, redactions, or visual evidence of experimental procedures. H. F. Fraser, ~I.D., C. F. Essig, :\I.D., & A. B. \Volbach, Jr., :'vl.D. Xution:al Instltult' o( \lc•nt:ll llt•nlth, ,\tltlh•tinn Hc•st•:trt·h Ct•nh•r I•.n.s. Hnsjlital, l.t•xinutun. l..:••ntm·ky .· ., ~/ Evaluation·~~ 9£ caris_oprodol . / and phenyramidol for adclictiveness Reprinted from Bulletin otr Nnrcotics (Vol. XIII, No.· 4, pp. 1-5, 1961}. -~ Evaltlation of carisoprodol and phenyramidol for addictiveness Dy II. F. Fraser, li.D., C. F. Essig, :u.D., & A. D. lVolhach, Jr., li.D. :'\ationnl Institute or llcnlnl lll'nlth. Addiction flcsl'nrch Ct'ntcr, P.II.S. lln!Opitnl, Lc:dngtou, Kcntucl.:y Carisoprodol (N-isopropyl-2-mechyl-2-propyl-1,.3-propane 2. Twenry-four-hour substitution of these drugs for mor diol dicarba.mate) is dosdy related to meprob:unate in che phine i.ri patients addicted to morphine. to ascert:Un their mical strUcture (1). It is a centrally acting skelet<tl "muscle effectiveness in preventing symptoms of abstinence from relaxant ", and is said to be particularly elfective in rele:lSing morphine (6). decerebr:tte rigidiry (1). In experimencl an'imals it produces 3. "Direct addiction ", which involves administration of high voltage, low frequency brainwave patterns and blocks these-.drugs in progressively increasing doses as tolerated for electroencephalographic activation (1). It is unique in th~t it 18 days (5) and/or stabilization on the maximum dosage is ineffective as an analgesic by nociceptive ·or withd4wal attained for an additional36 to -+3 da.ys. and abrupt withclr:lwal ref!e.x testS, but it is effective in counteracting pain produced of the drugs to ascert;1in whether pbysic:1l dependence develops by injection of silver nitrate into the joims of rats. Tllac it :1fter either 18 or 54· days of chronic administr:ltion. may affect the central perception of cercin forms of pain Ocher tests and specific deuils· will be described under each is suggested by behaviour of a dog subjected to painful stimu experiment. lation of an e."ttl'emiry. The animal wotdd withdraw the limb Part I. - Carisoprodol prompdy in response to painful ;cimulus, but would not 1. Effect of Si11gle Oral Doses in So11-adJicted Patients show dilatation of pupil usually noticed in response to pain (1). Evidence has also been provided that carisoprodol may elevate Methods. - Single doses of carisoprodol were administered the pain threshold in man using (a) high frequency electronic orally in capsules co fasting, non-coleranc addictS at 8. . 30 a.m., stimulation co the tooth (Margolin. 2) and (b) an ultrasonic and observations were carried out at hourly inccn·als for stimulus to induce deep, aching pain co the band {Holliday si..x hours, using the single-dose (a) high frequency electronic orally in capsules co fasting, non-coleranc addictS at 8. . 30 a.m., stimulation co the tooth (Margolin. 2) and (b) an ultrasonic and observations were carried out at hourly inccn·als for stimulus to induce deep, aching pain co the band {Holliday si..x hours, using the single-dose opiate questionnaires (patients' & Dille, 2). and observers' ratings). Phenyramidol (2-[Beca-hydroxyphenetbylamino] pyridine) Results.-Preli.mina.ry ~-periments indicted that doses is also a CNS acting muscle rel:ucanc, but in ·contradistinction below 1,000 mg induced no signi.fic:mc subjective effects, to carisoprodol, it is effective as an azulgesic by orthodo~ but with higher doses certain effects were demonstrated, as withdrawal refle.x tests, and irs potency in animals is compa shown in cable 1. It was not, however, until :1. dose o£2,000 mg rable to chat of codeine ·(12). TABLE 1" Both compounds are being marketed as muscle relax:mcs, Ertcets of single oral dos~s of cnriso[,rodol effective in the relief of pain due to muscle spasms (11, 2). (patient ratinns) Since both compounds represent new StructUral departures for analgesics, experiments were carried out at the Addic Dose tion Research Center to ascertain if either possessed mor (mg) phine-like addictive qualities in m:m. 4 1050 3 - " bl:mk " General methods .t - t~nquilliztt The subjects used in these srudies were healthy adult negro 1200 3-.. bl:lnk •• or \'(bite m<tles serving sentences for '\oiolation of state or 1-rcl=d federal narcotic laws, who volunteered for the experimentS. 1600 2-" blank·~ All were fomter opiate addicts. Since both drugs are being 1 - " dope ,. (2 of 6 resp<>nSC1) marketed for clinic:J. use by the oral rome, and since addictS would have difficulry extracting these drugs for injection 5 2000 2-" dope" from the inert ingredientS with which they are mi.xed, they 3 - barbitur:m.-s were evaluated or:tlly only. The tests employed to ascercin 15 2500 t - .. uope .. (2 of 6 r~-sponscs) addicth•eness were: 6 - b~rbicuratc:s 3-" bl:mk" 1. Administr:'Ltion of single doses to non-tolerant subjectS 1 - t><:nzc:drine for the detection of morphine-like elfr.:cts. Tlll.s was evaluated ~ - mi~cdl:mc:ous by mons of the: single dose opiate. q\lesrionnaires [patients' 5-slc:epy J. and obscrvt.:rs' r:ttings (7) 3 () ) was given that effects were consistently observed.· With 3 patients respeccivdy. All patients receiving morphine., ~vere 2,500 mg of orisoprodol, evaluated in 15 tests, only one of stabilized on 240 mg of subcutaneous The document is a declassified page from a research paper titled "Evaluation of carisoprodol and phenyramidol for addictiveness." It features several handwritten annotations, including a circled number "229" in the upper right corner and "Dr. Ispell" written next to it. At the bottom right, there is a handwritten alphanumeric code "B-399." The text itself is printed, listing authors and their affiliations. There are no photographs, stamps, forms, diagrams, or visual evidence of experimental procedures. The provided document is a page of text, not an image with visual elements. It contains no photographs, handwritten annotations, official stamps, filled-in forms, diagrams, schematics, organizational charts, or visual evidence of experimental procedures, equipment, or facilities. The content is exclusively textual, presenting research findings and methodologies related to the evaluation of carisoprodol and phenyramidol for addictiveness. There are no redactions or obscured content visible on this page. mons of the: single dose opiate. q\lesrionnaires [patients' 5-slc:epy J. and obscrvt.:rs' r:ttings (7) 3 () ) was given that effects were consistently observed.· With 3 patients respeccivdy. All patients receiving morphine., ~vere 2,500 mg of orisoprodol, evaluated in 15 tests, only one of stabilized on 240 mg of subcutaneous morphine sulfate dJi!y. 15 patients identified it as being " dope ".(opiate), and this ·The study was controlled in other tests, negatiyely, by substi patient identified it as such on only two of si."C observations. The tution of a placebo tor morphine, :md positively, by con predominate effectS subjectively :md oBjectively we.re similar tinuing the customary dose of morphine in the same subjects. to those of a barbitur:lte or alcohol, :md not similar to those ObServations for· intensity of abstinence were made hourly of an opiate. In contr:lSt to patients intoxicated with barbi from the 11th through the 2-tth hour .of abstinence (6, 3). turates and alcohol, none of the pati~ts who received large Since Clrisoprodol seemed to be b:ubiturace-like in many doses of carisoprodol were obstreperdus, belligercnr, silly or respectS, the study was also controlled by substituting intra difficult to manage. One or rwo hours <tfter 2,500 ing of muscular pentobarbital in an average dose of 1.11 grammes carisoprodol, most of the subjects bec:tme quite sle~y. some divided among five doses, in another experiment using 11 profoundly so, :md were difficult to arouse. They w'~re some ocher subjects. As in the preceding experiment, negative what confused when awakened, but did not show is much (placebo) :md positive (morphine) control tests were made dysarthria as one might anticipate from an equiYilent hyp at weekly· intet).-:tis in che same subjects. notic dose of barbiturates. All patients rhus affected, however, The comparative effectiveness of the various agents in were moderately ataXic. These effects disappeared almost suppressing abstinence was e'<"aluared by the paired t-cesc (3), completely in si."C hours. Carisoprodol, even in the highest using TAS values (total area scores) under the time-action doses, did not induce pupillarj constriction. curve for the 11 observations. 2. Twetzty-four-hour SubstillltioiJ of Carisoprodol for Jforpllit~e Results.-Carisoprodol partially but significantly (P < 0.03) Methods.-3,600 to 4,800 mg of carisoprodol (divided into suppressed symptoms of abstinence (figure 1), as tabulated by three equal oral dcses} was substituted for morphine in 6 and the hourly point score of Himmelsbach (8). Abstinence was 30 PLACEBO o I 25 317 TAS-163.9%. • The document contains three line graphs, each depicting the "Intensity of Abstinence - Hourly Points" over a "Hour of Substitution" period from 14 to 24, with a placebo group and a test drug group. The graphs show different drugs (Carisoprodol 4000mg, Pentobarbital 110mg, and Morphine 180mg) and their effects compared to a placebo. Below the graphs, a figure caption explains the visual data, referencing control groups, mean total areas under time-action curves, and statistically significant differences denoted by asterisks. The page also includes the number "4" in the top left margin, indicating it is page four of a larger document. but significantly (P < 0.03) Methods.-3,600 to 4,800 mg of carisoprodol (divided into suppressed symptoms of abstinence (figure 1), as tabulated by three equal oral dcses} was substituted for morphine in 6 and the hourly point score of Himmelsbach (8). Abstinence was 30 PLACEBO o I 25 317 TAS-163.9%. • o-o... ... • I; 20 .,. -o-i-• 0..... / l:i '·. o/'~ ~AMIOOL 1500mq . ~g~• TAS-149.4:17.7 . oJ 10 ~!<. s 30 25 PI..~E80 o 20 132 4:!:\7.5 /o'- / T.&.S- · o 0 15 ../. O ... o ,o ... ·-· .... • I • ;._./ 10 , MORPHINE 180m~-• -•/ o-o-0-~" PENTOBARBITAL H!Omq .TAS · · - 36 · .1 - ± · - 6. · 8 * 5 •-• ... •/ TAS-98J:!: 8.0 ...... ............... 14 16 18 20 22 24 14 16 18 20 22 24 HOUR OF SUJJSTITUTION Figure 1. Supprr.<si.•n •>f .1[J.<tillt1lU. 24-hour substitution fnr nwrphinc of c:~ri~nprodul. ph.:nyr~mjJ,,I. pcnto b.ubitJI, pbc~·bo, 2nd morphine (pn<itivc ~ontrol) concinU<:d in the <"U5t<ml:~ry dus:~~e. Compuisnm within individu:~-1 !,:Uphs ~rc ,·ros\-on·r. 2\"Cf;I~C rompari'<HI~ irt th•· ~:~me 9 subj•·,·rs. <'Xrc-pt in th..: C:lSC uf p<."m"b:~rbit~l. ± when 11 subj•·•ts wcr.: U.\l'd. T AS ihunbcr~ refer to< rh .: m.:~n coral ar•·2s und~:r the time-action cun·,·s st.m· d:ard error nf rlw nw~n. Si~-:nitkaur ditli:rc-m·•-s (I' 0.05) a~ compan:J tu l pb,·cbn an: shown hy an am·risk. ..• The total dos~~L· of ,•ac-h drug substimu:d to mpprcss symptoms nf ;lb,tincncc frum muq•hin.: i~ shuwn in mi lli~rJ umws. . ../ 5 also suppt"essed partially by pentobarbital (figure 1), but not h.'ld an additional EEG after 45 cbys on the drug. During to a statistically significant degree (P <.1 and >.05). The withdrawal, each of the 5 patients tlut lud taken carisopmJ~l 3 patients receiving the 4,800-mg substitution dose of c:uiso for 18 days h:ld an EEG 18 and 36 hours after the last dose. prodol were quite sedated and somewlut difficult to arouse, and the patient that lud carisoprodol for 54 d:t)'S l1:1J one but showed only a slight degree of dysarthria and ataxia. EEG 13 hours md another at 24 hours after the last do~c. All patients who received pentobarbital were sedated and Results.-During chronic administration of carisoprodol, showed a slight to moderate degree of at:>..xia and dysarthria; except for changes in the EEG pattern, the outstanding feature: . certain subjects were confused. was a complete absence of my The declassified document is a type-written page, with several instances of very small, dark, circular marks scattered throughout, most noticeably in the top right corner and near the middle of the page. The text itself is dense, and appears to be a scientific report or research findings. There are no photographs, handwritten annotations, stamps, forms, or diagrams visible on this page. The document seems to primarily consist of textual information detailing experimental procedures and results. 24 hours after the last do~c. All patients who received pentobarbital were sedated and Results.-During chronic administration of carisoprodol, showed a slight to moderate degree of at:>..xia and dysarthria; except for changes in the EEG pattern, the outstanding feature: . certain subjects were confused. was a complete absence of my significant subjective effec~s ev-en when the dosage was increased to 4,800 mg-daily. In 3. Di~ct Addidil)tJ to Carisoprodol other words, it was not possible co differentiate carisoprodol M~thods. - Five non-tolerant subjects were used in a from a· placebo (figure 1) . " single-blind " test -i.e., patients but not observers were Following abrupt wichdra wal of carisoprods:>l, the 4 patients unaware of the narure and schedule of _medication. Starch that received it for 18 days showed no autonomic signs of placebos and carisoprodol powder were ~epared in identi abstinence. and did noc realize tlut their medication had been cally appearing c:1psules, and all medication \\"as divided chan~d. TAS scores (total scores under the time-action equally :unong four doses daily. All patients initially recei\"ed curve during the 10 days of withdrawal) averaged 7i.3 during placebo capsules for 12 days, 4 received carisoprodol (or 18 withdrawal as compared with an average TAS score of days and one for 54 days. Carisoprodol was withch::lwn 41.0 observed duri.Qg their lase 10 da.ys on carisoprodol. This abn1pdy and replaced by identically appearing capsulc:S. The increase in the abstinence scores dur.ng withdrawal is insigni initial daily dose of carisoprodol was 1,200 mg;' this was ficant, particularly in ..,;ew of the face that the maximum incre:ued at a rate of 200 mg daily for 16 days to a daily daily score was only 10.3 points during withdrawal. The dose of 4,200 mg, and then by 300 mg" on the 1i th and 18th patient who received carisoprodol for 54 days showed no days, attaining a daily dose of 4,80(fmg. The patient receiving signs of abstinence when the drug was discontinued abrupdy; arisoprodol foe 54 days received 4,800 mg daily from the theTAS score was 38 points, and the maximum da.ily score 18th to the 54th day. w:s only 7 points. This patient likewise stated that at no time did he feel the medication, and he was completely unaware Observations were made three times daily throughout the · of the fact that carisoprodol had been discontinued. experiment, and the degree of abstinence was cal~ted by the daily The document contains two bar charts presented side-by-side, labeled "FEEL DRUG" and "IDENTIFIED AS 'DOPE'". Each chart displays four bars representing "CODEINE", "CARISOPRODOL", "PHENYRAMIDOL", and "PLACEBO", with the y-axis indicating "AVERAGE PERCENTAGE OF ANSWERS OF PATIENTS". Below the charts, there are labels for "Yes", "Don't care", and "No" with corresponding shaded and unshaded squares, suggesting a legend for a rating scale. A caption below the charts refers to "Figure 2. Ratings of patients during direct addiction tests." The image also shows some handwritten notations and a few circular stamp-like marks at the top. w:s only 7 points. This patient likewise stated that at no time did he feel the medication, and he was completely unaware Observations were made three times daily throughout the · of the fact that carisoprodol had been discontinued. experiment, and the degree of abstinence was cal~ted by the daily point scores of Kolb & Himmelsbach (10). In one The EEG pattern after single doses of 300 mg showed patient, evidence of physical dependence ''"as also ev-aluated (5) questionable barbiturate-like effects as compared with the by administering 2 mg of nalorphine subcutaneOusly on the pre-drug EEG, but after single doses of 1.000 and 2,000 mg, 44th day, and 5 mg on the 48th day of carisoprodol adminis and during chronic intoxication (4,200-4,800 mg daily), rration. Throughout the, test, patients and aides independently barbiturate-like effects were obtained. These changes consisted completed a chronic dosage opiate questionnaire (7) at 7 p.m. . of rhythmic and non-rhydunic low- and mediwn-voltage fast daily. Clinical toxicity was evaluated by obSI!n-ations and by activity (18-32 cps) seen more prominently in the frontal laboratory tests made prior to drug administratioiJ,.:md repeated leads. In the 4 men who received carisoprodol for 18 da.ys, at bi-weekly intervals, when carisoprodol was administered, the EEG patterns 17 and 36 hours after the last dose of the :s follows: routine analyses of urine, red and white blood cell drug were normal. In the case of the patient who took cariso COWlts, hemoglobin content, hematocrit and liver function prodol for 54 days, the first EEG, taken 14 hours after the tests (thymol turbidity cephalin fioccubcion. and evidence of last dose of carisoprodol, showed a barbiturate-like effecr, bilirubin in the urine). An electrocardiogram was made on but the one taken 36 hours after the last dose was normal. each patient while receiving placebos, and again after a high None of these patients showed focal oc generalized abnor dosage of carisoprodol lud been reached - i.e., 4,200 or malities of the paroxysmal cype during withdrawal, such 4,800 mg daily. as those seen following withdrawal of barbiturates (9, 13, 4). EEGs were obcined using an eight-ch:umel resistmce None of the clinical observations or laboratory testS showed opacibnce couplt.>d Gr:tSs apparatus. Using needle electrodes. significant deviations from pre-drug observations.· one bi-pobr and three mono-polar tracings (linked and Chronic administration of carisoprodol on a progressive grounded) were obt.1ined from fconcal, temporal. parieul dosage schedule did not induce a The document is a typed page of text, appearing to be a research paper excerpt, with no photographs, handwritten annotations, or stamps visible. The text is structured into sections with headings such as "Direct Addiction to Phenyramidol," "Methods," "Results," "Discussion," and "Summary and Conclusions," followed by a numbered list of references. There are no visible redactions, obscured content, diagrams, schematics, organizational charts, or forms with filled-in fields. The visual content is limited to the typed text and its layout on the page. resistmce None of the clinical observations or laboratory testS showed opacibnce couplt.>d Gr:tSs apparatus. Using needle electrodes. significant deviations from pre-drug observations.· one bi-pobr and three mono-polar tracings (linked and Chronic administration of carisoprodol on a progressive grounded) were obt.1ined from fconcal, temporal. parieul dosage schedule did not induce a c..~aracterisric barbiturate :md occipital areas (4) prior to administering drugs co the intoxication pattern (nystagmus. dysarthria. ataxia in gait and 5 patients used in this direct addicdon test. In 3 of these. the station. confueion, poor judgement and loss of emotional subsequent efft:ct of a single 300-mg dose of orisoprodol comrol), and when carisoprodol w:1s abruptly withdrawn. no W'-S ascertained about one hour after carisoprodol was adminis signs of barbiturate-like abstinence (anxicry. fine tremor, tered orally. In a simibr maJmc:r. chc effects of :1 sin~lc dose WC':lkm:ss, convulsions ami delirium) were observed (9). of 1.000 mg were determined in one: p:uient. and those of However. it remains to be st..'Cil whether aJministering cariso 2,000 mg in another patient. During the direct addiction test, prodol continuously in larger doses woukl induce a chronic EEGs: were taken. on all 5 patients one hour after che 10 a.m. state of imoxicuion. and whether abrupt wichJrawal under medication, when a daily dosage of 4,200 ot 4,800 mg had sucl1 circumst;1nccs wuuiJ provoke a barbiturate or mepro bern attained. The patiem receiving c:1risoprodol for 54 J;1ys bamate type of abstinence. Such a possibility is mggcsted -------- by the fact that carisoprodol is a congener of mcprobmute most impn.- . ssivc tinJing was an absence of detectable objec • and e."'<hibits many barbiturate-like pharmacological etfects. tive or subjective ph:mnJcological effects in these tests. 4 Purt 11. - I•h.-nyr:uuidol 2. 24-lwllr Substituti<'ll Plu:nyramidol for Aforphiue 1. Effects of Si11gle Doses Met/rods. - Tht.':ie were the same as those outlined for Methods,-These were the same as those described for carisoprodol. orisoprodoL • Results.-Phenyrami~lot in a total dosage of 1,50Q, mg · Results.-Seventeen. tests in a dose range of 100-730 mg (divided into three equal doses) was substituted for z-m. mg were conducted using non-tolerant subjects; 6 patients received of morphine sulfate in I) patients, and was compared with the rru.ximum dose of 750 mg. No etfects \vere reported after morphine (continued in che custonury dosage) and with a any of these doses by :my patient or observer, except sleepi placebo substituted in ocher tests using the same patiencs. of morphine sulfate in I) patients, and was compared with the rru.ximum dose of 750 mg. No etfects \vere reported after morphine (continued in che custonury dosage) and with a any of these doses by :my patient or observer, except sleepi placebo substituted in ocher tests using the same patiencs. lless, \vhich was noticed by one patient after a 730-mg dose. As compared widt a pl.1eebo. phenyramidol slighdy depressed symptoms of abstinence from morph.in~. but the degree of The pupils were not constricted. Neither the patients nor observers identified phcnynmidol as an opiate; in fact, the suppression was sratistically insignificam (figure 2} .. .... , .. FEEL DRUG " . IDENTIFIED AS .. DOPE •• 100 ..J ..J 80 ..J ..J 0 0 0 0 0 - 0 o 0 w 0 0 a : : : 0 ! 0 CD 60 a a : . : ~ <:: C w D z 0 a . a < : : : : w (.) 0 (J ) a > : : ( < . : ) : 0 lJ J a(J:) z > < ... : J : 40 C <: 2 : I z JJ . a .J . 0 (. ) < u X : I a J I . J : a. (.) : a I . : 20 0 100 ..J 80 ..J ..J 0 ...J 60 w z 0 g a a: . : 0 0 ~ < :: 0 C w D z w 0 0 a a: . : : 0 0 <X ! 0 C IJ D J 40 . . · .( 0 . I 0 . . J .. . . ) J · . . 0 ( a ( < J . : : ) ) : : a z : w > a I : . : : ( . a < . . : ) J . : . 0 0 ( W . ) ( 0 a ( < / . : : ) ) : : a : > z w a I : . : : ( . a < . . . : ) J . : . . .. .. 20 . . . . . . . . . . . 0 ... ... . ..... Yes Don't ore .. I:UL DAD .. "WOULD LIKE TO TAKE DAILY" Fi~;urc 2. R,uiugs : : ( . a < . . . : ) J . : . . .. .. 20 . . . . . . . . . . . 0 ... ... . ..... Yes Don't ore .. I:UL DAD .. "WOULD LIKE TO TAKE DAILY" Fi~;urc 2. R,uiugs <{ l'•'limts Juring Jirrct uJ,{iaicul lrsts. A cotnpJ.rison of the avc:ra!-:e perccm:~~e r•">p<>nses to the sin!!lc: dose qu~tium1aire (pati<·ncs' r:~tin!!s) for cnddm:, carisoprodol, ph,·nyr:unidol and .1 pb.:<·bo k>r the p:u:uneccrs" f,·d dnr!! ", " idcntitic:uinn as • Jnpc' ", " would like to takc d.1ily ",and " t~d bad ". The comparison betw•·en cod.·ine and a pl.•.:•·hu was made.: with the sJ.me >ul>_kccs in the s.:un•• c:xpcrimenc, but other comparison~ b..·cwl'l.'n drtl!!S were 111adc in anJlu!!OUS bur dirt~rL"!lt c:xpl'Tintcms using did~rcnt sub jet"!~. ·~· --- ' 3._ Direct Addiction to Plu:11 yrm11id"l face feel numb, I got a buzzing in both e:m, and [ had !nhtbll.' Methods. - Four non-!olcr:mt subjects were used in a double hearing." He also described :1 sensation at times rcscmblint.: effects of benzedrine or coc:Une, which would lase for nnlv blind test-i.e" neither p:~oticnts nor observers were :~.w:~.re a few minutes. On the. odtcr lunJ, he had a relaxed fed in~ of the nature :md schedule of medication. Swch placebo and when he laid quietly in bed. Since these cffcccs appcarc~l phenyr:unidol powder were prepared in identically appearing capsules. and all mediotion \'\':I.S divided into four equal contradictory to him, he inquired as to whether his mcJica tion had been changed from tinie to time. None of the patients doses daily. Initi:~.lly all p:~.tients rccc{ved placebo opsules for 7 to 10 days, chen :~.11 were given phcnyrarnidol for 18 day;s, liked the effectS of phenyrunidol, and the high incid~-nce of •• feel bad " reports as compared to the zero incidence of such· after which the drug was :~.bruptly wichdr:nvn for two d:~.ys. reports during chronic intoxication with codeine is uotc-· Medication was tl1en reswned for :m ;tdditiotul ~2 days. The worthy (figure 2). initi:ll d:tily dose of phenynm.idol w:~.s 600 mg, which was progressively incre:~.sed until a daily dose of 4,500 mg was After 61 days of chronic intoxiotion, none of these patients attained by the 18th d:ly, and an :l.ttempt \vas ffi;:Lde to subilize re:~.lizcd tlut pl:~.cebo capsules had been substituted. Abstinence patients on this do~ge for the renuinder of tl1e experiment. scores incre:~.sed until a daily dose of 4,500 mg was After 61 days of chronic intoxiotion, none of these patients attained by the 18th d:ly, and an :l.ttempt \vas ffi;:Lde to subilize re:~.lizcd tlut pl:~.cebo capsules had been substituted. Abstinence patients on this do~ge for the renuinder of tl1e experiment. scores were insignificant; in fact. they were smaller chan After a total of 61 days of chronic drug administration, comparably computed scores obtained while receiving phenyr:unidol was v:ithdr:m,1 on a douit.e-bl.ind basis by phenyramidol." replacing it with identically appearing plac~bo c:tpsules. Discussion Observations were the s:une as those nude for evaluating fn the tests employed, neither carisoprodol nor phenyra carisoprodol, except EEGs and EKGs were not obtaine?- midol showed any addictive properties of an opiate r:ype. ReSttlts.-One patient took phen•t"Tamidol for 16 days. The Although emsoprodol is pharmacologically similar in certain experiment was tecrnin:1.ted on the lith day, when :1. dosage respects to barbiturat"es, it is not as rapidly acting as certain of 4,200 mg had been attained, because he had diffuse'u rticaria. barbiturates. When the dosage of carisoprodol was rapidly Prior to this, the only symptom noted by this patient W3S increased from 1,200 to 4,800 mg daily within a period of .. sleepiness ". No symptoms or signs ofa bstinence developed 18 days, no evidence of intoxication was noted-suggesting after phenyr:unidol \Vas disconcinu;d, and the urticaria gra that some tolerance developed co the sechcive and hypnotic dually subsided. effects. The other 3 patients attained a daily dose of 4,300 mg by Summary and conclusions the 18th day, and when medication was withdrawn abruptly The addictiveness of orally administered carisoprodol and for two days they showed no evidence of absrinence. .M edica oeen phenyramidol Ius studied in fanner opiate addicts. tion was resumed on the 21st day, bur it was necessary to The procedures included effects of single doses, substitution reduce the dosage of r:wo pariems to 3,300 mg daily because tests to suppress abstinence from morphine, and direct addic of such complaints as indigestion, sleepiness, dizziness and tion tests. numbness of the skin (figure 2). One patient continued on 4,500 mg of phenyr.uni4oi daily, but he had a multiplicir:y It is concluded chat neither C:lri.soprodol nor phenyramidol of complaints; for examp . l e, ' h e st:~.ted •• . . It ffi;:Lde my possesses :1ddictive qualities of an opiate r:ype. REFERE:'i CES 1. BERGER. F. M., KLETZKIN, :\o-1., 4,500 mg of phenyr.uni4oi daily, but he had a multiplicir:y It is concluded chat neither C:lri.soprodol nor phenyramidol of complaints; for examp . l e, ' h e st:~.ted •• . . It ffi;:Lde my possesses :1ddictive qualities of an opiate r:ype. REFERE:'i CES 1. BERGER. F. M., KLETZKIN, :\o-1., LUDWIG, B. J., MARGOLIN, 8. HIMMELSBACH, C. K.: Studies of Certain Addiction Clur:tctCT S., & POWELL, L S.: Unus=l Mwde R.:lu:mc and .-'.n:llgesic istics of(a) Dihydtomorphine (" Pa~morplun "), (&) Dihydrodcsoxy Properties of N-Isopt"opyl-2-mcthyl-2-propyl-1,3-ptopancdiol Dicar morphiiK"-0 (" Dcsomorphinc: "), (c) Dihydrodesoxycodc:inc:-C banute (Drisoprodoi), ]. Ph.um.m1l. & E.xpcr. T1scap., 127: 66-73, (,. Desocodcine ''), and (d) Methyldihydromorphinone (" Metopon "), 1959. ]. Plr=n«ol. & E.-cpu. Tlu.-rap., 67: 239-2.;9, 1939. 2. Conference on NM-N.Jt,otic Dmgs f<Jr tire Relief ~f Pain and tlr.#ir .\lecltan 9. ISBELL, H., ALTSCHUL, S., KOR.NETSKY, C. H., EISENMAN, ism of Action (4-5 Dec. 1959). Ed. by F. M. Berger, Cluirm:in. Ann. A. J., FLANARY, H. G., & FRASER, H. F.: Chronic Barbiturate N.Y. A&ad. Sci., 86: (art. 1) 1-310, 1960. Incoxicacion, A.;\f.-i Arclr. Ncrr11l. &- Psyciliat_ •• 6-+: 1-28, 1950. 3. ED:\V ARDS, A. L.: Swistico1.L At14lpis for Students in Psyc/t(Jlogy atul 10. KOLD, L. & HIM.I'v1ELSBACH, C. K.: Clinicl Studies of Drug Education. New York:. Rhinciurt & Co., Inc., 1946. Addiction. IIt. A Critical Review of the \VichJ~wal Trocmcnts ~. ESSIG, C. F. & FRASER, H. F.: Elcc:trocnc:epiulogr:tphic Changes with Method of E~..UIUting Abstinence S)·ndron1cs, Am. }. Psycili.zt., in Mm during Use and \Vithd~wll of Darbitur:ucs in Moder:lte 94: 759-797, 1938. 5. D FR C$ A 1 S ge E , R E , E H C . F C! . i r & ~.