may article

8/8/2019 May Article

1/36

Drug and fikohol Dependence, 23 (1989) 183 - 218Elseiver Scientific Publishers Ireland Ltd.

183

The Committee on Problems of Drug Dependence:A legacy of the National Academy of Sciences.

A historical accountEverette L. Maya and Arthur E. Jacobsonb

Department of Pharmacology and Toxicology, Medical College of Virginia, Virginia Commonwealth University, Richmond,VA 23298-0613 and bLaboratory of Medicinal Chemistry, National Institute of Diabetes, DigQShVQ and Kidney D~SQ~ZSQS,

National Instit utes of Health, Bethesdo, MD 20892 Il7.S.A.)

(Received March 20th, 1989)

The history of The Committee on Problems of Drug Dependence is traced from its beginning (1929) as The Committee onDrug Addiction to 1989, its sixtieth anniversary. A brief account of the etiology of The Committee from The Bureau of SocialHygiene, established in New York City by John D. Rockefeller, Jr. in 1913 is also given.

Key words: physical dependence potential; abuse liability: narcotic analgesics and antagonists; agonist/antagonists; stimulantsand depressants; animal and human testing; drug addiction and evaluation.

Introduction

The purpose of this article is to review thehistory of the Committee on Problems of DrugDependence (CPDD). This history was

undertaken on the recommendation of CPDD,acting on the suggestion of its Chairman, Dr.Mary Jeanne Kreek, in order to summarize andthen update the detailed history presented inthe volume The National Research CouncilInvolvement in the Opiate Problem (1928-1971) by Nathan B. Eddy, published by TheNational Academy of Sciences [l]. Of particularconcern and interest are the years that fol-lowed the termination of sponsorship by TheNational Research Council in 1976 and the tran-

sition years that culminated in the structuringof an incorporated committee affiliated withseveral highly regarded scientific societies. Theauthors have been closely associated withCommittee activities since 1960 (E.L.M.) and1974 (A.E.J.), principally as coordinators of thetesting program for evaluating the physicaldependence potential and abuse liability ofanalgesics and other compounds, and asmembers of the Board of Directors and Execu-

tive Committee. It is hoped that the achieve-ments of the CPDD since its inception (1929)will be well focused and that this history willgive insights into contributions of CPDD tosolutions of drug-dependence problems.

Although the principal source of material forthe period ending in 1971 was that of reference1, CPDD minutes, reports and proceedingswere consulted frequently, especially after1971.

Beginnings - The Committee on DrugAddiction

The origin of the Committee on Problems ofDrug Dependence is traceable to the Bureau of

Social Hygiene established m New York City in1913 by John D. Rockefeller, Jr., to promoteresearch in the general field of social hygienewith especial emphasis on criminology. How-ever, because of the increasing problem ofabuse of drugs*, particularly narcotics, and

*A special committee of investigation in 1919 arrived at afigure of 100 000 addicts (including cocaine abusers) in theUnited States.

0376-8716/89/)03.50 0 1989 Elsevier Scientific Publishers Ireland Ltd.Printed and Published in Ireland


2/36

184

pressure from the public and the medical pro-fession, the Bureau was urged to get involvedin the area of drug abuse. Consequently, theBureau of Social Hygiene established a Com-mittee on Drug Addiction, whose notable

accomplishments have been previously setforth in a scholarly treatise, The NationalResearch Council Involvement in the OpiateProblem, authored by Nathan B. Eddy andpublished by the National Academy of Sciences[ll.

In 1928, the newly appointed Director of theBureau of Social Hygiene, Lawrence B. Dun-ham, reassessed the Bureaus involvement inthe drug-addiction problem and proposed to theNational Research Council, National Academyof Sciences (NRC, NAS) that this body acceptfunds from the Bureau for the support of ascientific investigation of narcotic drugs to becarried out under the auspices of the Division ofMedical Sciences (DMS).

Accordingly, Dr. Charles White, then Chair-man of DMS, with the aid and advice of foureminent members of the NRC, Drs. ClaudeHudson and F.B. Laforge (chemistry) and Drs.Reid Hunt and Carl Voegtlin (pharmacology)laid the groundwork for the formation of a newCommittee on Drug Addiction which first meton January 12,1929 as a Temporary AdvisoryCommittee on Drug Addiction. Dr. White wasChairman ex officio. The discussions of thisgroup centered on elaboration of a programwhich would include: (1) the analysis of thechemical and biological literature of the addic-tion alkaloids; (2) the formulation of rules andregulations for the legitimate use of alkaloidshaving addiction properties and the educationof physicians and the public on the knowledgeof these rules by means of medical schools,scientific societies and drug-manufacturingfirms and (3) the replacement of all present useof addicting alkaloids by substitutes having noaddiction properties. The discussions broughtforth two subjects for research: (1) therelationship between morphine and codeine (in-cluding possible dissociation of adverse andbeneficial effects) and (2) the cocaine addictionproblem. Little, if anything, was done at that

time to address the latter problem, perhapsbecause the abuse of cocaine had waned consid-erably following the introduction of the(synthetic1 substitute, procaine.

The DMS under the Chairmanship of Dr.

Ludwig Hektoen (pathologist), who succeededDr. White as chairman of DMS on June 30,1929, expanded the membership of the Tempo-rary Advisory Committee on Drug Addiction,to include the following: Chairman, WilliamCharles White, Consultant Pathologist,National Institute of Health and Chairman,Committee on Medical Research, NationalTuberculosis Association; Charles W. Edwards,Professor of Materia Medica and Therapeutics,Chairman, Department of Pharmacology, the

University of Michigan; Ludwig Hektoen, Path-ologist, Director, John McCormick Institute ofInfectious Diseases; Claude S. Hudson, Chief,Division of Chemistry, National Institute ofHealth; Reid Hunt, Professor of Pharmacology,Harvard Medical School; Frederick B. LaForge,Senior Chemist, Bureau of Entomology andPlant Quarantine, U.S. Department of Agricul-ture; Torald Sollman, Dean, School of Medicineand Professor of Pharmacology, WesternReserve University; Walter L. Treadway,Assistant Surgeon General, Division of MentalHygiene, U.S. Public Health Service; CarlVoegtlin, Pharmacologist, Director, NationalCancer Institute, National Institute of Health;Harry J. Anslinger, Commissioner, Bureau ofNarcotics, U.S. Treasury Department andLawrence Kolb, Assistant Surgeon General,Division of Mental Hygiene, U.S. Public HealthService.

This committee served without change until1939. Its first meeting was held on November 3,1929 with secretarial assistance from Mrs. Dor-othy Nicolson and Mrs. Mary Goodwyn, daugh-ters of Chairman White.

Early Scientific Program (1929-1939)

Ultimately, the Committee decided upon aresearch plan that involved three components- chemical, pharmacological, and clinical. Thechemical effort, under the direction of Dr. Lyn-


3/36

185

don Small, a young, talented, Harvard-trainedalkaloid chemist (who had also studied in Ger-many for 2 years) was begun at the Universityof Virginia in the autumn of 1929. Small, withhis modest staff of pre- and post-doctoral stu-

dents, was concerned principally with chemicalmodifications of the phenanthrene-type alkal-oids (morphine, codeine, thebaine and neopineloccurring in opium. A complementary programon total synthesis of structures vaguely resem-bling morphine and congeners was directed byErich Mosettig, Ph.D., a young organic chemistdrafted by Small from Professor ErnstSpaeths laboratory, University of Vienna,Austria. Mosettig also had a small group of pre-and post-doctoral students, of which one of theauthors (E.L.M.) was privileged to be a smallpart from 1935 - 1939.

Nearly a year later (June, 19301, when theneed for pharmacological examination becamepressing, Nathan B. Eddy, M.D., Cornell Uni-versity, who had practiced medicine briefly butwho, at the time, was teaching physiology andpharmacology at the University of Alberta,Edmonton, Canada was appointed to direct thepharmacology program at the University ofMichigan in the laboratory of Dr. CharlesEdmunds (previously mentioned Committeemember).

Eddy, who had spent the 2 previous yearsworking in the laboratory of Dr. Robert Gesellat the University of Michigan, was made Asso-ciate Research Professor of Pharmacology. Hebegan baseline animal studies of morphine andcodeine covering acute toxicity and effects onpain, circulation, respiration, the G.I. tract andthe CNS as reflected in overall behavior (excite-ment, sedation, convulsant action). Dr. Eddysstaff at Michigan in 1932 included Drs. H.M.Kruger, Charles I. Wright and R.H.K. Foster,the first in physiology at Michigan and theother two from the Universities of Rochesterand Chicago, respectively. During his tenure atMichigan, Dr. Eddy also began one of his majorroles in the Committee, that of liaison, with vis-its to the University of Virginia and other cen-ters of activity.

Dr. Margaret Sumwalt of the Department of

Pharmacology, Womens Medical College ofPhiladelphia, joined the staff later while Drs.Erwin E. Nelson and Ralph Smith of Dr.Edmunds departmental staff complementedthe efforts of Eddys group. Assistance was

also provided by several pre-doctoral and medi-cal students.The clinical arm of The Committees pro-

gram began to develop about 1934 under thedirection of Clifton K. Himmelsbach, M.D., ayoung commissioned officer of the PublicHealth Service from The University of VirginiaMedical School. Himmelsbach, who wasrecruited by the aforementioned Dr. Treadway,had received research training on tolerance andphysical dependence to morphine in rats atWestern Reserve University under Dr. TaroldSollmann and later, at Michigan, with Eddy. Dr.Himmelsbach began his studies with prisoneraddicts at the Penitentiary Annex of the FortLeavenworth, Kansas, Prison. This unit wasshortly thereafter transferred to Lexington,Kentucky. Members of the Himmelsbachresearch team included Drs. Edwin G. Wil-liams, Howard L. Andrews (later to spendmany productive years at NIHl, Fred W.Oberst and Ralph R. Brown. Among the sub-stances tested by Himmelsbach (1934- 1935)were codeine, isocodeine, pseudocodeine,dihydrodesoxymorphine-D (desomorphine, anew substance from Smalls laboratory1 anddihydromorphine, all previously studied inanimals by Eddy and his colleagues.

The achievements of the first decade ofCommittee sponsorship can be summarized asfollows. Nearly 500 compounds (the majority ofthem new) were supplied by Small, Mosettigand their colleagues for evaluation in animals.Three of the most promising ones, a totally syn-thetic compound, a tetrahydroisoquinolino-phenanthrene, desomorphine and 5-methyl-dihydromorphinone (metoponl were studied inhumans not only for dependence liability butalso for pain relief. Metopon was judged to bemore potent (especially orally) than morphinewith less physical and psychological depen-dence liability but manufacturing problemsprecluded its distribution for general clinical


4/36

186

usage. Nevertheless, important structure-activity relationships evolved and Himmels-baths basic studies for assessing tolerance andphysical-dependence liability remain as a modelof excellence. In addition to the studies in

humans conducted at Fort Leavenworth andLexington, clinical-efficacy trials were carriedout at University Hospital, the University ofMichigan by Drs. Boys, Logie and Becker (in19381 under the supervision of Dr. Eddy, at ThePondville Cancer Hospital in Massachusetts,The Massachusetts General Hospital, at WalterReed Army Hospital (Washington, DC.1 and atThe Marine Hospital in Baltimore. In additionto Himmelsbach, a key individual in the efficacytrials was Dr. Lyndon Lee, educated at theUniversity of Virginia and Duke University.Lee, after training with Himmelsbach, wasrecruited principally to test metopon. While atPondville he conducted definitive clinicalstudies on morphine and desomorphine. Heremained active in the analgesics area for some40 years and maintained a liaison role withCPDD from the vantage point of VeteransAdministration (VA) hospitals.

From 1929 - 1932, funds for Committee oper-ations ($50 OOO/yearl were supplied by theBureau of Social Hygiene. For the remaining 7years, a direct Rockefeller Foundation grant(again $50 OOO/yearl supported the work of theCommittee.

World War II hiatus

Although successes with metopon, whichhad definite advantages over morphine [l] andthe totally synthetic isoquinolinophenan-threne, codeine-like in analgesic potency andessentially free of abuse liability (which how-ever elicited unexpected human toxicity1 [l]gave cause for optimism, it was obvious thatthe goals set forth by the Committee in 1929had not been attained by 1939. Thus, plans forcontinuation of the scientific program weremade as soon as it became apparent that Rocke-feller funding would not be continued beyond1939.

Through the influence of several people, par-

ticularly Dr. Charles White and PHS SurgeonGeneral Thomas Parran, Smalls group andEddy joined forces at the National Institute ofHealth (NIH) to resume their attempts todevelop safe morphine and codeine substitutes

in close association with the PHS Hospital inLexington. In the meantime, the Committee onDrug Addiction held its last meeting on Janu-ary 29,1939 and recommended to DMS that itcontinue a Committee on Drug Addiction in anadvisory capacity (to PHS).

Ultimately (early in 19401, an advisory com-mittee was appointed. It consisted of threemembers of the 1929- 1939 committee: CharlesWhite, Chairman, Harry J. Anslinger andLawrence Kolb. Dr. Small succeeded Dr. Kolbin 1945 and Dr. Eddy was added as secretary in1946.

Due to World War II, however, the efforts ofEddy, Small and Mosettig were diverted to thesearch for new antimalarials soon after thecombined move to NIH. Nevertheless, partlyby dint of encouragement from Dr. Eddy andthe Advisory Committee, partly due to theemergence of totally synthetic analgesics (e.g.,pethidine, methadone and the morphinans)from Germany and Switzerland and partlybecause of sustained interest in metopon, clini-cal studies were continued at Lexington underthe direction of Himmelsbach. Dr. Himmels-bath transferred to NIH in 1944 and was suc-ceeded as director of the Lexington facility byDr. Harris Isbell who had served as an intern atthe Lexington Hospital (1934 - 19351 and was astaff member at NIB until 1944. In addition, Dr.Abraham Wikler from the Staten Island Mar-ine Hospital joined the Lexington group as aneurologist in 1940. Without a doubt, their fun-damental finding that the synthetic analgesics(pethidine, methadone et al.) had dependencepotential comparable to morphine was a primefactor in the strict control of these early syn-thetics. These synthetics had, at first, beenpublicized as having minimal abuse liability asmorphine-like narcotics [2].

Other notable contributions of the AdvisoryCommittee and the chemical-pharmacologicalresearch group during the war years were: (1)


5/36

187

introduction of metopon, particularly for oraluse in chronic pain. Financial support (a meto-pon fund) was provided by grants from theAmerican Cancer Society ($50001, Parke-Davisand Company and Sharpe and Dohme ($2500

each) to aid in the production and distributionof metopon; (21 preparation of a final report (byDr. White) of the Committees activities. Thisreport consisted of a very large number ofreprints and publications from the several par-ticipating chemical, pharmacological and clini-cal laboratories and was published by the NRC[3] and (31 he publication of three detailed mon-ographs, The Chemistry of the Opium Alka-loids [4], Studies on Drug Addiction [5] andThe Pharmacology of the Opium Alkaloids [S].

It should be recorded here, too, that in June,1939, Small and Eddy were jointly therecipients of the first Scientific Award of theAmerican Pharmaceutical Manufacturers Asso-ciation.

A fresh start - The Committee on DrugAddiction and Narcotics (1947-1965)

With the rapid influx of totally syntheticagents from Europe after the war and in consid-eration of ever-present problems of drug addic-tion in general, Dr. Lewis H. Weed, theChairman of DMS, deemed it essential to form anew committee on drug abuse issues. Hisactions were based on requests from SurgeonsGeneral of the Army and Navy, inquiries fromcommercial firms and increasing emphasis onthe work of the United Nations germane topublic health. A further stimulus was a reportbrought back from Germany by a governmentalcommittee headed by E.C. Kleiderer onresearch done there from 1935-1944 towardthe production of totally synthetic analgesics[7]. One of the most interesting compoundsdescribed in the report was methadone (thencalled amidone), which, its structural dissimilar-ities notwithstanding, mimicked morphine inalmost every aspect of its pharmacological pro-file.

The new committee was named the Commit-tee on Drug Addiction and Narcotics @DAN).

Drs. Isaac Starr, Professor of TherapeuticResearch, University of Pennsylvania, Schoolof Medicine and Nathan B. Eddy, PrincipalPharmacologist and Medical Officer, NIH, wereappointed Chairman and Secretary, respec-

tively. Other members of this new committeewere as follows: Honorable Harry J. Anslinger,Commissioner of Narcotics, U.S. TreasuryDepartment; Drs. Raymond N. Bieter, Profes-sor and Head, Department of Pharmacology,University of Minnesota Medical School: DaleC. Cameron, Senior Surgeon and AssistantChief, Division of Mental Hygiene, U.S. PublicHealth Service; Walter Palmer, Director, ThePublic Health Research Institute, City of NewYork; Maurice H. Seevers, Professor and Head

of the Department of Pharmacology, TheUniversity of Michigan Medical School andLyndon F. Small, Chief, Laboratory of Chemis-try, National Institutes of Health. Drs. Starrand Eddy continued in their respective rolesuntil June 30, 1960. Administrative detailswere handled by members of the professionalstaff of NRC.

The first meeting of the newly appointedcommittee was on October 2, 1947 at NAS,Washington, D.C. Present at this meeting wereliaison representatives from the Army, Navy,FDA and the American Medical and DrugManufacturers Association. Also attendingwere Drs. Weed, S.D. Aberle, D.C. Leary, Hay-den C. Nicholson and Mr. John J. Lentz, Jr.,representing the NRC. It was the intent of theCDAN to maintain association with these andother organizations with mutual concerns.Later, liaison was established with the WorldHealth Organization (WHO) and the AddictionResearch Foundation of Toronto.

At this time the supervised distribution ofmetopon was under way and would continue for1 year. Attention was also given to developinga protocol for the international control of syn-thetic narcotic drugs not covered by conven-tions then in force. The principles of theprotocol were comparable to those of theHarrison Act (also known as the Opiates Act).The Committee endorsed these principles andthe protocol (later known as the Paris Protocol


6/36

188

of 19481 was ratified by the U.S. It provided forthe same control of synthetic substances as forthose of natural origin by the Geneva Conven-tion of 1931.

From 1948- 1955, a total of 15 business-sci-

entific meetings of the CDAN were convened.After 1955 (with the exception of 1960 when theCommittee met in January and April), scientificmeetings were held annually, a practice whichhas continued to the present. The NAS-NRCpublished the proceedings of these meetings asminutes through 1968, as reports through1974 and finally as proceedings in 1975 and1976, when NRC relinquished sponsorship. The1977 and 1978 proceedings were published bythe Committee on Problems of Drug Depen-

dence, Inc. Starting in 1979, the proceedingshave been published as part of the ResearchMonograph Series of the National Institute onDrug Abuse (NIDA) and are archival. Before1979 they were labeled non-archival

The second and third meetings of the Com-mittee on Drug Addiction and Narcotics were,like the first, convened at NAS, WashingtonD.C., January 14,1948 and May 17.1948. At thesecond meeting, such items as (1) efficacy andcontrol of methadone isomers; (21 the study ofpapaverine, a naturally occurring constituentof the opium plant; (31 evidence and timerequired to establish sufficient addiction liabil-ity to initiate narcotics control: (41 testing of K-4710 (ketobemidone, a new Demerol analog1 atthe Addiction Research Center (ARC); (51 clini-cal testing of methadone and its antipodes (atthe Massachusetts General Hospital) and (61testing of peyote at ARC and mescaline inmonkeys at the University of Michigan, werediscussed. One scientific paper was also pre-sented - The Addiction Liability of SomeDrugs of the Methadone Series and of 6-Methyl-dihydromorphine by H. Isbell and Anna J.Eisenman. The major issue at the third meetingwas a discussion of three research proposalsseeking support from CDAN. Because of inter-est in supporting such types of proposals,efforts were made to establish a research fundby contacting 100 members of the AmericanDrug Manufacturers Association and 74 mem-

bers of the American Pharmaceutical Manufac-turers Association. Based on the repliesinvitations were sent to 29 drug-manufacturingfirms to a meeting with the chairman and secre-tary of CDAN and Dr. Small. Seventeen

accepted and sent representatives to Washing-ton, D.C., on July 1, 1949. At this meeting, itwas decided to invite representatives of inter-ested firms to meet with CDAN wheneverresearch reports were to be presented and torequest the Executive Committee of NRC toauthorize CDAN to solicit, accept and adminis-ter funds for research on analgesia and addic-tion. Authorization for a sum of $50 000 wasgiven by NRC July 26,1949 and, in September,Dr. Detlev Bronk, Chairman of NRC wrote to

26 drug firms inviting their support. Therewere 14 prompt replies. By the end of 1949,eight firms had contributed $18 500. Industrialsupport increased gradually until 1970 when 51firms (eight of them foreign) donated $198 225for the year. Also discussed at the third meet-ing was the possibility of clinical trials of anal-gesics in VA hospitals. These clinical studieswere initiated some 15 years later and becamean important part of the activities of the CPDD.In addition a report on K-4710 (ketobemidone,107201 from the ARC was presented andrecorded in the minutes.

The PHS hospital at Lexington, Kentuckywas chosen as the site for the fourth meeting ofCDAN, on October 15 and 16,1948 to show theCommittee the facilities of the hospital andmeasures employed for evaluating physicaldependence. Dr. Henry Beecher (Massachu-setts General Hospital) was invited to attendthis meeting to describe his studies of analgesiaand sleep in post-operative patients which wassupported by a U.S. Army contract.

In line with the advisory functions of theCommittee, medical research programs of theArmy and VA were examined and recom-mendations made. The Committee also author-ized a letter to the producer of ketobemidone,Winthrop Stearns, Inc., that stated that thisdrug, based on the results of studies conductedat Lexington, has addiction potentialitieswhich are highly dangerous and that clinical


7/36

189

application is not advisable at this time. TheCommissioner of Narcotics and the FDA wereapprised of this recommendation which wasaccepted by the producer.

In November, 1949, March, 1950, January,

1951, June, 1951 and January, 1952, the fifth toninth meetings of CDAN were held at NAS,Washington, D.C. Dr. Erwin E. Nelson who hadattended the first two meetings as an FDA liai-son representative was appointed to the Com-mittee in the fiscal year 1948-1949 and Dr.Joseph N. Hayman, Jr., Dean of Tufts MedicalCollege replaced Dr. Palmer in 1949.

The Committee was called upon frequentlyfor evaluation and recommendations concern-ing the efficacy and dependence-producing

properties of such drugs as ketobemidone,dihydrocodeinone (hydrocodone, Dicodid, Hyco-dam, dihydrohydroxycodeinone (oxycodone,Eucodal, Nucodan, Percodanl, ( + l-&hydr-oxy-N-methylmorphinan (Dromoranl andalphaprodine (Nisentil, NU-11961, a potentDemerol (pethidinel analog. Based on resultsfrom studies conducted at Lexington, all ofthese drugs were judged similar to morphineregarding dependence-producing properties.

The possibility of establishing a monkey col-ony to perform preliminary studies on potentialdependence-producing drugs at the Universityof Michigan was first suggested by Dr. Seeversat the fourth meeting of the Committee, Octo-ber, 1948. However, his formal proposal wasnot considered until 1950 at the sixth meeting.The overall plan was to conduct studies in rhe-sus monkeys using procedures similar to thoseemployed at Lexington for the study of addic-tion liability in humans. The first formalreports from Dr. Seevers project (partiallysupported by the research fund) appeared inthe minutes of the ninth and tenth meetings,both of which were held in 1952.

By 1950, there were sufficient funds from thepharmaceutical industry to partially supportstudies by Dr. Henry K. Beecher (Mas-sachusetts General Hospital) whose objectiveswere (11 to determine the potency of analgesicagents against post-operative pain by a double-blind technique, comparing the effects of these

agents with those of a placebo and the standarddrug, morphine and (2) to evaluate the sideeffects in normal subjects of placebo, morphineand the experimental agent, randomlyadministered at weekly intervals.

During this period the Committee was askedto review and make recommendations on suchmatters as: (11 Armed Forces Medical SupplyList; (21 the replaceability of opiates by avail-able synthetic analgesics; (3) the work of WHOand its role in international control; (41 the dif-ferences among isomers in the acetylmethadoland morphinan series; (51 the development ofantagonistic capabilities of nalorphine [8], thefirst strong, specific opioid antagonist devel-oped (at Merck and Company in the early

1940s); (61 the demonstration of the develop-ment of tolerance and physical dependence tobarbiturates; (71 he mortality of opium addictsin Taiwan; (81 he status of national and interna-tional control of narcotics; (91 criteria for clini-cal trial and (101 the physicians handling andcare of the drug addict. Opinions and recom-mendations were rendered on all of theseissues.

Meanwhile, chemical research by the Small-Mosettig group at NIH was redirected towarddevelopment of improved substitutes formorphine and codeine and efforts to make theU.S. independent of products from opium. Allfour of the above-mentioned acetylmethadoloptical isomers, along with the correspondingracemates, were prepared and evaluated atNIH [9], Michigan and, in some instances atLexington. Beginning about 1948, Eddyimproved and refined the Wolff-MacDonald,hot-plate method of testing for antinociception[lo] and began coordinating the NAS-spon-sored, drug-testing program. The coordinationof the drug testing program of the CPDD haspersisted to the present at NIH.

In addition to compounds submitted by theSmall-Mosettig group, the pharmaceuticalindustry and later, universities and otherresearch institutions contributed compoundsfor preliminary testing by the hot-plate proce-dure for antinociception. When warranted, fur-ther testing at Michigan in monkeys was


8/36

recommended. More promising compoundscould then be considered for study in humans atLexington and/or clinical trial for analgesic effi-cacy.

The tenth meeting of CDAN was held at the

University of Michigan, Department of Phar-macology, June, 1952 in order to observe theaddiction studies in monkeys. The effects ofmorphine, ketobemidone, Dromoran [( f l-3-hydroxy-N-methylmorphinan], methadone, iso-methadone, 6-methyldihydromorphine andnalorphine were shown (in morphine-dependentmonkeys) live and on film.

At this meeting, the Committee discussedthe action of dextromethorphan (the O-methylderivative of the analgesically inert deztro-isomer corresponding to Dromoranl and itspotential as an antitussive agent (possible cod-eine substitute for cough). Also, an opinion ren-dered earlier by the Committee that all needsfor morphine and related opiates for sympto-matic pain relief could be met by then-availablesynthetics, was reiterated in response to arequest from the Munitions Board in referenceto the stockpiling of opium.

The ARC, Lexington, Kentucky was againthe site for CDANs eleventh meeting in Janu-ary, 1953. Drs. Isbell, H.F. Fraser (who hadbeen transferred to ARC from NIH in 19491 andWikler demonstrated: (1) the abstinence syn-drome after prolonged administration of mor-phine and attempts to relieve symptoms withsynthetics; (2) the effects of prolonged adminis-tration of a new synthetic thiambutene (IC-501,distantly isosteric with methadone; (3) induc-tion of abstinence with eserine (physostigmine)in morphine-dependent, spinal dogs; (41 abruptand nalorphine-induced withdrawal; (51 effectsof drugs and cycles of addiction and withdrawalon the electroencephalogram; (61 effect of mor-phine and of barbiturates on anticipatory anxi-ety associated with pain and (71 abstinencesyndromes after withdrawal of barbiturates oralcohol.

Committee meetings that included presenta-tion of research reports and participation ofinvited representatives from the pharma-ceutical industry had occurred over the pre-

vious 3 years (1951-19531. It was time, itseemed, to decide whether this type of programwas worthwhile and what changes, if any,should be made in the Committees activities.Overall, it was decided that its program wassound but that rather than becoming a screen-ing facility, the Committees efforts should beoriented toward research studies designed tocontribute basic knowledge especially for thepharmaceutical industry.

Concretely, it was suggested by Dr. Isbellthat Dr. Beechers clinical trials include nalor-phine-morphine combinations and nalorphinealone as a control, This suggestion to use nalor-phine, the only clinically useful narcotic antago-nist known at the time, was based on the ideathat it might counteract the side effects ofmorphine in humans. Dr. Isbells suggestionwas, perhaps, promulgated by a discussion ofDr. Eddy with the group at ARC in the late1940s about nalorphine. Dr. Eddy noted duringthat discussion that if the antagonism werereally specific, the result of the administrationof nalorphine to a person in whom dependenceof the morphine type had been established,should be the same as for abrupt withdrawal ofmorphine and an abstinence syndrome shouldemerge. Nalorphine was not, prior to this time,known to have analgesic action. The research(carried out by Drs. L. Lasagna and Beecher)resulted in the important finding thatnalorphine itself was an effective analgesic forhumans with post-operative pain. Nalorphine,then, became the first known narcotic agonist-antagonist. It was not, however, clinicallyuseful for analgesia due to its side effects. Theeventual utility of the original idea of Drs.Eddy and Isbell to test a mixture of an analge-sic and an antagonist is discussed later, in theAnimal testing section.

The theme of the twelfth meeting, held inBoston in November, 1953 at the Massachu-setts General Hospital in the historic EtherDome (where anesthesia was first demon-strated publicly), was analgesic testing in ani-mals and humans. Attendance (761 was thelargest yet and all attendees were entertainedat dinner by two pharmaceutical firms. This


9/36

191

sponsorship gave rise to a discussionconcerning propriety. With the understandingmade known to the companies that no obliga-tion was implied, it was considered acceptableto receive such amenities.

Current methods of analgesic testing werepresented at this meeting along with the test-ing of drug mixtures, especially those forcough. The discussion of drug mixtures whichcould be useful as substitutes for codeineprovided the stimulus for another symposium,on antitussive action. The symposium was heldduring the thirteenth meeting in January, 1954.The initial half day of the thirteenth meetingwas at the Merck Institute for TherapeuticResearch in Rahway, New Jersey. The meeting

continued in the afternoon at the Hoffman-LaRoche Research Laboratories, Nutley, NewJersey and concluded the following day at theNew York Academy of Sciences.

In addition to the description of methods forproducing cough in animals developed at Merckand Roche, reports were presented by Drs.Beecher and H.A. Bickerman, Columbia Univer-sity, New York on their attempts to produceand measure cough in human volunteers. Alsopresented were reports by Dr. Seevers (mon-key studies with coded compounds) and Dr.Isbell on research at ARC. At this meetingthere was a discussion of research that theCommittee might support if more funds becameavailable. The studies mentioned were: (11 bar-biturate addiction studies; (2) patient response(analgesic, subjective) to placebos; (3) difficultyof antitussive studies using volunteers and (4)the psychological aspects of the use of anal-gesics.

The fourteenth meeting of the Committeewas another occasion for on-the-spot observa-tion. This meeting was held on October 1 and 2,1954 at the Sterling-Winthrop Research Insti-tute, Rensselaer, New York, where factoryproduction of Demerol was shown. Addiction tomeperidine (Demeroll, as revealed by admis-sions to the hospital at Lexington, wasreported and the film, The Slave, was pre-sented. It was noted that medical and paramed-ical personnel were most susceptible to

addiction to meperidine, possibly because of itsavailability to them.

Three new compounds were considered atthe fourteenth meeting. One was the stronganalgesic, 14-hydroxydihydromorphinone (Oxy-

morphone, Numorphanl. The other two weresynthetics, propoxyphene and heptazone - thelatter closely, the former distantly relatedstructurally to methadone.

At this meeting in 1954, the Committee alsoadopted a resolution which, in effect, expresseddisapproval of a proposal by the New YorkMedical Society to establish clinics to dispensenarcotics to addicts (with precautions), whichwould be in reality a quasi-legalization of theirdistribution. This was an unequivocal rejection

of maintenance therapy, an attitude that was tochange some 15 years later, as is well known.For its fifteenth meeting, CDAN met again

in Lexington, Kentucky, at the PHS Hospital inJanuary, 1955. Various aspects of treatment ofaddicts were discussed. Continued support ofSeevers and Beecher was approved, as was anew grant for analgesic studies at Sloan-Ket-tering Memorial Institute, New York by Dr.Raymond Houde. Also, an application from Dr.Lyndon Lee at Wayne County Hospital, Detroitfor clinical studies of analgesics was approvedin principle. These applications followed anannouncement in Science (November, 19541that CDAN might have available limitedresources for support of research on analgesiaand addiction. Included in this announcementwas a request for information on basic researchbeing carried out in these areas, so that theCommittee might serve as a center forexchange of information on current investiga-tions in analgesia and addiction. Incidentally,this was the only meeting from 1930-1971 notattended (due to illness1 by Dr. Eddy.

From September, 1955 to February, 1965meetings 16-27 (two in 19601 of CDAN wereheld (for dates and sites, see Appendix 3, Table2 of Ref. 1). Changes in membership during thisperiod were as follows: Dr. Marshall Gates,Chairman of The Department of Chemistry,University of Rochester succeeded Dr. Smallwho died in 1957. Added to the Committee the


10/36

19 2

same year was Dr. Jonathan Cole, formerly amember of the NRC professional staff andChief of th e Psychopha rm acology Cent er ofThe National Institute of Mental Health. Drs.Cameron an d Nelson resigned in 1958 and were

repla ced by Dr s. Ralph Sm ith (FDA), men tionedpreviously and Henry Brill of the New YorkState Department of Mental Health and Direc-tor of The Pilgrim P sychia tr ic H ospital on LongIslan d. Mr. Anslinger resigned from t he Com-mittee in 1959 and, although close liaison withThe Bureau of Narcotics was maintained, hewas not replaced by anyone from the Bureau.Dr. Starr, whose t enure as Chairman was thelongest (13 years) ever, s tepp ed down (butremained a Committee member until 19691. Hewas replaced as Chairman by Dr. Eddy for 1year only (19611, becaus e he (Dr. Edd y) wasma de a professional ass ociat e of NRC an d (offi-cially) designat ed E xecut ive Secret ar y ofCDAN, duties which he had been performingfor several years. Dr. Cameron who served onth e Comm itt ee from 1947- 1958 an d again in1961, becam e Cha irma n in 1962, a position h eheld until 1967 when h e resigned to a ssum e th eoffice of Chief, Drug Dependence, WHO,Geneva, Switzerland. In this position he main-tained close ties with the Committee until hisretirement from WHO (19751. Other new mem-bers of th e Comm ittee in th e next 3 years were:Ever ett e L. May, Ph.D., Chem ist, Chief, Sec-tion on Medicinal Chemistry, NIH; IsidorChein, Ph .D., Psychologist, New York Un iver-sity Graduate School of Arts and Sciences;Francis N. Waldrop, Ph.D., Behavioral Scien-tist, St. Elizabeths Hospital, Washington, D.C.;Harris Isbell, M.D., Clinical Pharmacologist,Department of Medicine, University ofKentucky Medical Center, who had retiredfrom P HS in 1963; and Robert Str au ss, Ph.D.,Behavioral Scientist, University of Kentucky.Dr. Chein ret ired in 1964 after serving for 2years.

The d ecade from 1955 to 1965 was probablyamong the most event ful in the Committ eeshistory. Growing awareness of and interest in,the scientific sessions were reflected by anincreasing attendance and diversity of reports

presen ted especially from 1961-1965. A sub-scription dinner became an established customalong with an after-dinner sp eaker presenting alecture of general interest to the attendants.

The research fund grew steadily from anan nu al cont ribut ion of $39 000 in 1955 (one for-eign, 26 domest ic firms cont ribu tin g) to $85 349(four foreign , 33 domes tic) in 1965. Th is wa ssupplement ed by ann ual cont ribut ions from theVA ($5000-$75001 and WHO ($20001 beginningin 1961. Consequent ly, grant applicat ions andfunding increased. These are all described indet ail on pp. 74-79 of Ref. 1. Most of th e proj-ects were fun ded for 1- 5 years, but su pport ofDrs. Seevers and Houde continued throughoutth e lo-year period an d for man y years beyond.

New, noteworthy drugs evaluated by CDANdur ing th is period were propoxyphene (a dis-tant relative of methadone); the hexa-methyleneimines (e.g., ethoheptazinel; thebenzimidazoles (e.g., etonitazenel; the 6,7-ben-zomorph an s [ll] (which spawn ed, among oth ers,ph ena zocine, S KF 10047 an d cyclazocin el; fen-tanyl, and the antidiarrheal compound, diphen-oxylate. Also, dihydrocodeine, marketed inEu rope for m any years as an ant itussive agent,was tested clinically for analgesic efficacy byBeecher an d was foun d to be effective with m in-ima l side effects . Several of th ese dr ugs a re inmedical use today and ar e cont rolled as na rcot-ics part ly a s a result of the findings an d recom-mendations of CDAN. Two drugs which werenot controlled at that time, dextropropoxy-phene (Darvonl, the (+ l-isomer of propoxy-phene an d penta zocine (Talwinl, th e latt er, th efirst agonist-antagonist to he used clinically,were cont rolled later. In fact it was during t hisdecade that the basic laboratory research ofArcher , Ha rr is et al. [12] an d the clinical stu diesof Beecher , Keat s, Las agna et a l. [13] paved th eway for t he heightened inter est in and th erapid development of the agonist-antagonisttype analgesics.

Specific opioid antagonists developed by thepharmaceutical industry and tested thoroughlyby CDAN from 1957 - 1965 were levallorph an ,a nalorphin e-like morph inan d erivat ive; a pur eantagonist, naloxone UV-allylnoroxymorphonel


11/36

193

and its orally effective, longer-acting, cyclo-propylmethyl analog, naltrexone. These threecompounds along with nalorphine have been ofinestimable value in the dependence studies atMichigan and Lexington. They have also been

important drugs in clinical practice and havestimulated a great deal of basic research in thereceptor area. Naltrexone was finally approvedfor clinical use by the FDA in 1984.

It was during this period, too, that seminalanalgesic-efficacy studies by Houde, Wallen-stein, Rogers et al. [14] became models of excel-lence and that clinical trials by the VA underthe direction of Dr. Lyndon Lee on potentiallyuseful analgesics were begun. This period (1955-1965) was also characterized by ack-

nowledgement of the importance of the monkeycolony at Michigan not only as a first-classscreening facility but which was also rapidlydeveloping into a laboratory of excellence inmany aspects of basic research on analgesics,their antagonists and the agonist-antagonists.Assisting Dr. Seevers in this effort weregraduate students, Samuel Irwin and GeraldDeneau, who received their doctoral degrees inthe Department of Pharmacology, Universityof Michigan.

The Bureau of Narcotics and the FDA wereincreasingly seeking the advice and recommen-dations of CDAN on efficacy and abuse liabilityof potentially marketable drugs. From time totime resolutions and statements were issued bythe Committee regarding narcotics control,treatment of addiction and replaceability ofcodeine and other opiates by synthetics. Theabuse of psychotropic substances such as theamphetamines, tranquilizers, etc. wasdiscussed from time to time but no researchwas sponsored by the Committee in thisregard. In 1963 the Committee co-authoredwith The Council on Mental Health, AmericanMedical Association, a paper, Narcotics inMedical Practice: The Use of Narcotic Drugs inMedical Practice and The Medical Managementof Narcotic Addicts [15].

Finally, some important changes in person-nel at ARC should be noted. Drs. Isbell andWikler retired in 1963 to accept positions at the

University of Kentucky, while Dr. Fraser wentto Eli Lilly. This would have been a crushingblow were it not for the appointment of Dr. Wil-liam Martin (who had joined ARC in 1957) withM.S. and M.D. degrees from The University of

Illinois, to succeed Isbell as Director and thehiring of Charles Gorodetzky (M.D., BostonUniversity School of Medicine, Ph.D., Univer-sity of Kentucky) and Donald R. Jasinski (M.D.from The University of Illinois, Chicago) in 1963and 1965, respectively. These three maintainedthe splendid scientific tradition established bytheir predecessors.

The Committee on Problems of DrugDependence (1965-1976)

In 1964 the WHO Expert Committee on Ad-diction-Producing Drugs met to discuss (amongother subjects) terminology relating to drugabuse. Objections to the term addiction hadbeen expressed by Isbell (who preferredchronic intoxication) as early as 1956 and bySeevers (1962) who alluded particularly to theeffects of amphetamines as psychotoxic. TheExpert Committee ultimately recommendeddrug dependence as a substitute for drugaddiction and drug habituation with a modify-

ing phrase to indicate the drug type (e.g., mor-phine type, cocaine type, etc.). The CDANaccepted this recommendation and officiallychanged its name to Committee on Problems ofDrug Dependence (CPDD) on July 1, 1965, atitle which more accurately reflected a broad-ening scope of interests.

From 1966 to 1973 contributions from thepharmaceutical industry increased from$101 850 to nearly $200 000 (51 domestic andeight foreign firms), leveled at the latter figurethrough 1973 and gradually declined there-after. These funds were supplemented from1961-1970 by contractual and grant moniesfrom the VA, Office of Civilian Defense, FDAand WHO (whose last contribution of $2000 wasin 1966). From 1971-1976, contributions alsocame from The Bureau of Narcotics and Dan-gerous Drugs (BNDD), The National Instituteof Mental Health and The National Institute onDrug Abuse (NIDA).


12/36

194

Needless to say, the grants program flour-ished during the halcyon funding years of 1966to 1973, principally in the clinical area. Investi-gators included, in addition to the redoubtableRay Houde and his capable associates, Stanley

Wallenstein and Ada Rogers, such outstandingresearchers as Henry K. Beecher, LouisLasagna, Arthur Keats, T.J. De Kornfeld, L.J.Cass, F.F. Snyder, T.J. Kantor and the VAstudy group (Lyndon Lee, Richard Paddock,J.W. Belleville, William Forrest, Colin Brownet al.1 [16]. Those funded in the basic researchareas included R. Aston, L.S. Harris, H.L.Grumbach, R.T. Harris and G.A. Deneau. Dr.Deneau, Senior Investigator in Dr. Seeversdependence studies in monkeys from 1954-

1965, assisted by S. Weiss, established a dogcolony dependent upon sodium barbital, forassessing the abuse potential of hypnotics andsedatives. Deneau set up a similar Beagle-dogcolony at The Southern Research Institute inBirmingham, Alabama and reported to theCommittee through 1971[17].

Noteworthy, too, is that (11 in 1969, CPDDheld its first (joint) meeting with The Commit-tee on Alcohol and Drug Dependence, Councilon Mental Health of the AMA at Palo Alto; (21in 1970 the first interim meeting of the execu-tive committee was convened to allow moretime for discussion of special problems and (31in 1971 CPDD met outside the United Statesfor the first time (in Toronto, Canada at TheAddiction Research Foundation).

At the first interim meeting, functions ofCPDD were redefined by Dr. R. Keith Cannan,Chairman of DMS-NAS from 1953- 1967 andExecutive Secretary of CPDD from 1967-1970. These functions included support of theAnnual Meeting and publication of itsproceedings, the screening and evaluation pro-grams and the grants program. CPDD alsofunctioned in an advisory role to The Bureau ofNarcotics.

Peak attendance (459) at the annual scientificmeetings was reached in 1970 at The HiltonHotel in Washington, D.C., February 16-18.Complete and accurate information on time,place and attendance of meetings (to 19711, on

resources (to 19701 and on the grants program(to 19721 are given in Tables 2, 3 and 4,respectively, of Ref. 1.

During 1965- 1976 (especially the lateryears) CPDD continued to advise The Bureau of

Narcotics [later becoming the Bureau ofNarcotics and Dangerous Drugs (BNDD), thenthe Drug Enforcement Administration (DEA)]and FDA on various aspects of drugdependence. It again aided The Council onMental Health, AMA, in revising (1967, 1971)[15] the 1963 statement on Narcotics in MedicalPractice. Included were recommendations onthe Nyswander - Dole Methadone Mainte-nance program [18]. In collaboration with theAMA Committee on Alcoholism and Drug

Dependence, it drafted a resolution on mari-huana (see Ref. 1 therein, p. 1161 and provided atask force which issued a report to FDA regard-ing the abuse potential and hazards of drugcombinations (Ref. 1, p. 119). A Statement onTesting for Dependence Liability in Animalsand Man was prepared and made an Adden-dum to the Minutes of the 28th meeting in 1966.At the request of The United Nations Divisionof Narcotics, this was published in The UnitedNations Bulletin on Narcotics in 1969. A com-pletely revised statement was published in1972 [19].

In 1971 attention was again focused onreplaceability of the narcotic analgesics andantitussives from natural origin. The opinion,that opium was expendable, was againexpressed.

In 1967 Dr. Eddy (who had retired from butremained a consultant for NIH in 19601resigned as Executive Secretary and was suc-ceeded by the aforementioned Dr. Cannan. Dr.Eddy also relinquished management of the test-ing program to one of the authors (E.L.M.1 butremained a member of CPDD until 1971 and aconsultant until his death in 1973. ExecutiveSecretary Cannan was succeeded by Mr. DukeTrexler, an employee of NAS, in 1971. Mr.Trexler, assisted by an associate executive sec-retary, Dr. Ralph Smith who had for manyyears been associated with committee activi-ties, served until the end of NAS sponsorship in


13/36

195

Table I. Members of the Committee on Problems of DrugDependence and Consultants in 1972.

H. Frank Fraser, ChairmanD.C. Trexler, Executive Secretary (NRC)R.G. Smith, Associate Executive Secretary (NRC)

Henry Brill Harris IsbellJonathan 0. Cole Lewis J. SargentDaniel X. Freedman Cecil G. ShepsLeo E. Hollister Klaus R. UnnaRaymond W. Houde E. Leong WayMilton H. Joffe Chris Zarafonetis

ConsultantsNathan B. Eddy Everette L. MayWilliam R. Martin Maurice H. Seevers

Table III. Members of the Committee on Problems ofDrug Dependence and Consultants in 1974.

Leo E. Hollister, ChairmanD.C. Trexler, Executive Secretary (NRC)R.G. Smith, Associate Executive Secretary (NRC)

Jonathan 0. Cole Beny J. PrimmDaniel X. Freedman Lee N. RobinsRaymond W. Houde Cecil G. ShepsDonald R. Jasinski E. Leong WayMilton H. Joffe Chris Zarafonetis

ConsultantsHenry Brill Everette L. MayH. Frank Fraser Maurice H. Seevers

At the time of the Annual Meeting for the denoted year. Table IV. Members of the Committee on Problems ofDrug Dependence in 1975.

1976. The members of the CPDD from 1972 to1976 are listed in Tables I - V.

Regarding chairmanships, Dr. Henry Brill, amember of CPDD since 1960, became chairmanin 1968, succeeded, as stated before, by Dr.Eddy for 1 year. Dr. H. Frank Fraser, wellknown for his distinguished career at NIH,ARC and Eli Lilly, also served for a single year,followed by Dr. Leo Hollister, a member ofCPDD since 1969. An outstanding medicalinvestigator from the VA Hospital, Palo Alto,Dr. Hollister functioned very effectively in thiscapacity through the difficult transition yearsto be addressed below.

Table II. Members of the Committee on Problems of DrugDependence and Consultants in 1973.

Leo E. Hollister, ChairmanD.C. Trexler, Executive SecretaryR.G. Smith, Associate Executive Secretary (NRC)Jonathan 0. Cole Lee N. Robins

Daniel X. Freedman Lewis J. SargentRaymond W. Houde Cecil G. ShepsDonald R. Jasinski Klaus R. UnnaMilton H. Joffe E. Leong WayBeny J. Primm Chris ZarafonetisHerbert A. Raskin

ConsultantsHenry Brill Everette L. MayH. Frank Fraser Maurice H. Seevers

Leo E. Hollister. ChairmanD.C. Trexler, Executive Secretary (NRC)R.G. Smith, Associate Executive Secretary (NRC)Daniel X. Freedman Jack H. MendelsonLouis S. Harris Beny J. PrimmRaymond W. Houde Herbert A. RaskinArthur E. Jacobson Lee N. RobinsDonald R. Jasinski Cecil G. ShepsMilton H. Joffe (deceased) Travis ThompsonEverette L. May Klaus R. Unna

Table V. Members of the Committee on Problems of DrugDependence in 1976

Leo E. Hollister, ChairmanD.C. Trexler, Executive Secretary (NRC)R.G. Smith, Associate Executive Secretary (NRC)Daniel X. Freedman Beny J. PrimmLouis S. Harris Herbert A. RaskinRaymond W. Houde Lee N. RobinsArthur E. Jacobson Cecil G. ShepsDonald R. Jasinski Travis ThompsonEverette L. May Klaus R. UnnaJack H. Mendelson

At the University of Michigan [20], the mon-key-dependence studies were in the capablecharge of Dr. Julian Villarreal from 1967-1973. Dr. Villarreal a medical doctor from Mex-ico City, Mexico, received the Ph.D. degreefrom the University of Michigan (in 1969) andhad assisted Dr. Deneau for a year until the lat-ter moved to Birmingham. From 1973- 1974,


14/36

196

Henry H. Swain, M.D. assisted him and becameth e prin cipal investigat or from 1974 - 1978,followed by James H. Woods, Ph.D., who ispresently in charge of the group.

At t he thirty-fourt h ann ual meeting of

CPDD held on Mar ch 22- 24, 1972 at t he Un i-versity of Michigan, Ann Arbor, John E. Inger-soll, Director of BNDD, in his forma l rem ar ks t oCommitt ee at t endants stat ed, that drasticallyreducing the availability of heroin is our majorobjective, while genera lly implying th at t heabuse of narcotics was reaching major propor-tions. Fur th er emphas izing this, he called atten -tion to the establishment of the White HouseSpecial Action Office on Drug Abuse Preven-tion, headed by Dr. J erome J affe (an eminentinvestigator in drug abuse) and to themethadone maintenance program and treat-ment programs tha t J affe was implementing.

Following the Michigan meeting, BNDD con-sidered the heroin-abuse problem so seriousthat this body negotiated a contract with NAS-CPDD to conduct a study concerning the use ofsynthetic substitutes for the opiate narcotics inmedicine and the possibility of banning opiumproduction. Consultants chosen for this studywere Dr s. Louis H arr is and Joseph Cochin. ta l-ented researchers in drug abuse an d intimatelyassociated with CPDD activities. Their survey(from December 1972 to Ma rch 19731 ult imatelyinvolved the AMA and the results were pub-lished by Th e Dru g Abuse Coun cil, Inc., 1828 L.Str eet, Washington, D.C. 20036, un der t he t itle,Synthetic Substitutes for Opiate Alkaloids: AFeasibility St udy. The summ ary stat ementwas as follows: Ther e is reason t o believe th atbanning of opium production will notsignificantly affect problems of narcotic abuseeven if adequate substitutes for the opium-

derived drugs were available.There were at least t wo oth er n ota ble event s

at t he 1972 meeting. One was th e present at ionof a paper by Dr. William Martin and VirginiaSan dquist of ARC, ent itled Long-Acting Na r-cotic Anta gonist s. They suggested th at suchantagonists or depot preparations of antago-nists might provide blockade of the usualheroin effects and thus could be a treatment

modality for heroin abuse. Their findings havebeen explored with enthusiasm and someclinical su ccess. Th e second event of espe cialnote at th e 1972 meeting was th e convening ofth e first sat ellite conference at a CPDD annu al

meeting. This session on drug self-administra-tion (Chairm an , Dr. J am es H . Woods of Dr.Seevers group) led to a CPDD-sponsored work-shop held in Febru ar y, 1973 on Sta nda rdizat ionof Self-Administration Techniques in Animals.The chairmen were Drs. Duncan McCarthy ofThe Parke-Davis Company, Ann Arbor, Michi-gan and Woods. The proceedings of this work-shop were published in the first newsletter ofThe International Study Group InvestigatingDrugs as Reinforcers (ISGIDAR) in August,1973. This group ha s continu ed to convene sa t-ellite meetings at each an nua l meeting of CPDDand undoubtedly helped pave the way for inclu-sion of the testing of stimulants and depres-san ts as a part of CPDDs broadened inter estsand activities in 1988. Fu rt herm ore, severaldistinguished members of ISGIDAR (Drs.Woods, Schuster, Balster, Brady, Mello, Men-delson, Thompson, Gr iffith s et al.) eventu allybecame valuable members of the CPDD.

Ear ly in 1973, Dr. Nath an Browne E ddy wh oha d been th e kingpin, th e major dr iving force ofthe Committee almost from its inception (andespecially from 19471, died p eacefully in hissleep after a full workda y of scientific and oth eractivities. It was fitting and timely, therefore,th at at the May 21- 23,1973 ann ual meeting inChapel Hill, North Carolina , Chairman Leo Hol-lister a ppointed an ad h oc committ ee (Seevers,Brill and Fra ser) to establish a N ath an B. EddyMemorial Award. This committee sent its rec-ommendations to Dr. Hollister on August 10,1973 providing for an an nu al awa rd ba sed on

contributions to the drug abuse field either foran un usu ally import an t discovery or for tota lcontributions over the entire career of therecipient. The a ward, to be presented at th ean nu al meet ing, was t o consist of a gold meda land a cash prize of $2500 plus travel expenses.Also recommen ded were an Interna tiona lAward Committee of six persons to be selectedby CPDD to serve a 3-year term and a goal of


15/36

19 7

$75 000 to be obtained th rough solicita tionsfrom manufacturers, friends of Nathan Eddyand attendees at recent and possibly futureCPDD meetings. The recommendations inessence were accepted and appropriately t he

first E ddy awardee was Dr. Seevers at thean nu al meet ing of CPDD, held in Mexico City,Mar ch 14 - 17, 1974. The 1975 an d 1976 recipi-ent s of th e awa rd were ARC-Un iversity ofKentucky stalwarts, Harris Isbell and Abra-ha m Wikler, respectively. The subsequen tawa rdees ar e list ed in Table XXV.

In execut ive session at th e 1969 meet ing inPa lo Alto, it was noted th at r eport s from Michi-gan on monkey-dependence studies were beingissued 8- 12 months after receipt of com-

poun ds. This lag was due n ot only to an increas-ing rate of submission of compounds but also tothe more sophisticated and exhaustive testsbeing made, in turn a reflection of changes inthe pharmacological profile of the new drugs,par ticularly th e agonist-ant agonists.

To ensure more prompt reporting and togenerally complement th e Michigan program, aprimate colony modeled after that at Michiganwas ultima tely established in 1973 at The Medi-cal College of Virginia (MCV) of Virginia Com-monwealth University under the direction ofDr. Louis S. Harris (assisted by Dr. W.L.Dewey, for many years a collaborator at Ster-ling-Winthrop Research Institute and The Uni-versit y of Nort h Car olina ) who, a year ear lierhad been appoint ed Chairm an , Depart ment ofPharmacology at MCV. Dr. Mario Aceto, whohad joined the MCV staff from Winthrop, wasin charge of the day-to-day testing-researchoperations and another MCV staff member Dr.Robert Balster, recruited from Duke Univer-sity in 1973, sup ervised self-admin istr at ionstu dies on dr ugs of special int erest. Fina ncially,the MCV program was made possible becausefirst BNDD and then the National Insti tute ofMental Health assumed support of the Michi-gan studies. Ultimately (starting in 19781, heNational Institute on Drug Abuse (NIDA)provided most of the financial support for boththe Michigan and the MCV primate programsto which was later added (at MCVl rodent-infu-

sion tests for dependence potential. The coordi-nation of effort and agreement of results incases of deliberate duplication have beenrema rka ble and gratifying. In ret rospect th ismove was timely because it coincided with the

gradual slowdown and ultimate cessation(December 31,19761 of hum an test ing for abu sepotential at ARC. It was important to have amore complete a nimal test ing program tocompensa te for th e lack of huma n data.

The last a nnu al meeting of CPDD to be heldat N AS wa s in May, 1975. Atten dan ce (445) atthis meeting was the second largest in the his-tory of The Commit tee. In addition to the th ree-day scientific program, four coordinate satellitemeetings were scheduled. At the executive

session (May 181, a goal of $100 000 was set asprincipal for the Eddy award. At this session,also, th e groundwork was laid for a conferenceon prediction of abuse liability of stimulant anddepressant drugs. Such a conference, convenedat NAS April 19-21, 1976, was spons ored byCPDD, NAS-NRC, DE A, FDA a nd NIDA wit hrepresentatives of some thirty pharmaceuticalfirms in attendance. Co-chairmen of the confer-ence were Drs. Travis Thompson and KlausUnn a of The U niversity of Minn esota and Uni-vers ity of Illinois, Chicago, res pectively, bothmem bers of th e Executive Commit tee ofCPDD. Pa rt icipant s were intern at ionally r ecog-nized investigators in drug abuse. Theproceedings, t itled Pr edictin g DependenceLiability of Stimu lant an d Depressan t Drugs,were published by University Park Press,Balt imor e, London, Tokyo, 1976. Co-edit orswere Th ompson and Unn a. This was a valuablesupplement to the previously mentionedpublication (recently revised a second time)Testin g for Dependence Liability in Anim alsan d Ma n [19].

The deat h kn ell of NAS s ponsorsh ip of CPDDwas sounded a t i ts interim m eeting at th e NASbuilding, Febru ar y 26, 1976. Cha irma n Hollis-ter made public the contents of a letter (datedDecember 9.19751 writt en to him by Thomas J .Kenn edy, M.D., Execut ive Dir ector of Th eAssembly of Life Sciences, NRC-NAS. Inessence the let ter stated that the Executive


16/36

198

Committee of the Assembly of Life Scienceshad voted to discontinue sponsorship of CPDDby approximately June 30, 1976. This decisionwas based on the recommendation of a VisitingCommittee appointed by NRC-NAS to review

various aspects of the Academy-Committeestructure.Despite the consternation caused by this

decision, the Committee began immediately todebate other possibilities for continuation of itsactivities, feeling unanimously that CPDDserves an essential purpose in the nationalinterest and the agencies that have providedsupport in the past have, in informal discussion,expressed their wish to continue support.

Of the eight possibilities considered, incorpo-ration of CPDD as a separate entity wasdecided upon. Thus, it was declared that CPDDwould be incorporated under the laws of theDistrict of Columbia, by June 30, 1976 if possi-ble. This was not achieved, whereupon NASagreed to extend sponsorship to February,1977. Along with incorporation would be solici-tation of a consortium of 8 - 10 highly regardedscientific societies with interest in drug abuse;each society would name one of its members toserve on a Board of Directors.

The NAS also agreed to publish the Proceed-ings of the Annual Meeting to be held in Rich-mond, Virginia and to lend its good offices tothe solicitation of funds for the fiscal year 1977.The NAS aided in every way possible theattainment of an orderly transition.

At the last NAS-sponsored annual meetingof CPDD (hosted by The Medical College ofVirginia, Virginia Commonwealth University)in June, 1976, three satellite meetings wereheld: Conference on Naltrexone, Chairman, Dr.Julius Demetrios, Division of Research, NIDA,Rockville, Maryland; Drugs as Reinforcers,Chairman, Dr. Charles R. Schuster, The Uni-versity of Chicago; Session on Drugs as Dis-criminative Stimuli, Chairman, Dr. John A.Rosecrans, MCV. There were over 400 inattendance at this meeting. In addition to aplenary session at which Dr. Abraham Wiklergave the Eddy-Award address, some 52 scien-tific papers were presented, Following a

reception and banquet dinner, scholarlyaddresses were presented by Dr. Jerome Jaffe,then Professor of Psychiatry, College ofPhysicians and Surgeons, Columbia University,New York and Dr. Robert L. DuPont, Directorof NIDA.

Among the last drugs to be tested at, ARC inhumans were meptazinol, nalbuphine, bupren-orphine, butorphanol, propoxyphene napsylate,propiram fumarate and tilidine. Most of thesedrugs were also tested for clinical efficacy byvarious CPDD grantees, principally by RayHoudes group and the VA. Most are nowmarketed.

Post NRC - an independent, incorporatedcommittee (1976-1989)

The two extraordinary events whichoccurred late in 1976 deeply affected the futurecourse of the CPDD. The traumatic effects ofthe loss of the human testing facilities at theAddiction Research Center (ARC) in Lexing-ton, Kentucky (due to a moratorium on prisonerresearch declared by the Federal Bureau ofPrisons) and the loss of NAS-NRC sponsorshipcolored the events of the following severalyears as well as the contemporary activities ofthe CPDD. These incidents heralded the begin-ning of a tumultuous decade in the life of theCommittee.

Upon retrospective evaluation, it was real-ized that the impact of the CPDD on the humantesting facilities at Lexington had appreciablylessened during the past several years, coinci-dent with the ARCs status as the intramuralresearch arm of NIDA. NIDA had been man-dated to test only those compounds which wereof interest to the U.S. Government (not neces-sarily compounds which might be marketed bythe pharmaceutical industry and for which theCPDD perceived a need to determine abuse lia-bility in human subjects with the thought thatthese new opioids might pose a public healthproblem). Furthermore, the ability of the CPDDto influence or even suggest which compoundsmight be evaluated at the Lexington facilityhad lessened considerably since Dr. Eddysdeath. Thus, the CPDD, coincident with its


17/36

199

incorporation as a separate entity, began asearch for an alternative to the Lexington facil-ities.

The activities of the Committee followingincorporation were complex and extensive.

These activities are grouped for purposes ofdiscussion int o: (1) incorpora tion an d reorgan i-zat ion, (21 pu rposes an d goals, (31 animal t est ing,(41 hum an test ing, (51 relationships with U.S.Government and international organizations,(6) fun ds a nd awa rds an d (71 conversion to amembersh ip organization.

Incorporation and reorganizationThe first meeting of the wholly independent

Committee on Problems of Drug Dependence,

Inc., was h eld at t he In tern at iona l Inn in Wash-ington, D.C., in Februa ry, 1977. The pr imar yobjective was to organ ize th e CPDD, Inc., an dto elect officers for th e new corpora tion to meetthe legal requirements for the Committee toact as an independent entity under a consor-tiu m of professional societies.

The init ial and cont inuing r eorganization ofthe CPDD will be presented in a simplifiedmanner. It may, even so, seem complexbecau se, since incorpora tion in 1977, th e CPDD,Inc., had to modify its by-laws many times toenable the organizational structure to best fitits needs. The apparent complexity wasconfoun ded by two facts : (1) The r et ent ion ofthe word Committee in its name. After incor-porat ion, th e Committ ee became in fact a Cor-poration, but the old word was retained. Thus,an Execut ive Comm ittee, various sta nding andad hoc committees and subcommittees of theComm itt ee wer e event ua lly form ed; (21 Therapid evolution of the CPDD, Inc., in itsat tempt to increase the depth and the breadthof its views far beyond those encompassed bythe original CPDD, before incorporation. Pres-ently, at least four new members are elected tothe Board each year (as noted below, the pre-sent-day Board is the combination of an Execu-tive Committee and a Board of Directors), andthis serves to infuse new views and thoughtsinto its actions.

The CPDD, Inc., in 1977, divided it s st ru c-

tu re int o an Execut ive Commit tee a nd a Boar dof Directors. These two groups constituted theCorporation, and the offices of President of theCorporation and Chairman of the Board werecreated. Although these could have been, in

principle, two separate individuals, in fact theCha irma n of th e Boar d of Directors served asthe President of the Corporation. New mem-bers of the Executive Committee were electedfrom a list of candidates selected by a subcom-mittee and each member of the Board ofDirectors was a representa tive of a profes-sional society, appointed (with the concurrenceof th e Execut ive Commit tee) by th at society.The professional organizations were called theAffiliated Societies of the CPDD, Inc.

Dr. Leo Hollister was elected Cha irma n ofthe Executive Committee and Dr. TheresaHarwood the Executive Secretary of theCorporation, at the time of incorporation. Dr.Hollister was succeeded as Chairman of theExecutive Commit tee in Ju ly, 1977, by Dr. Dan-iel X. Fr iedman. Dr. Hollister t hen served (un tilJ uly, 1979) as th e Ch airma n of th e Board ofDirectors. The members of the Committee andth e init ial four Affiliated Societies at th e timeof incorpora tion ar e noted in Table VI.

Table VI. Members of the Committee on Problems ofDrug Dependence, Inc., and Affiliated Societies in 1977.

Leo E. Hollister, ChairmanTheresa Harwood, Executive SecretaryDaniel X. Freedman Beny J. PrimmLouis S. Harris Herbert A. RaskinRaymond W. Houde Lee N. RobinsArthur E. Jacobson Cecil G. ShepsDonald R. Jasinski Travis Thompson

Everette L. May Klaus R. UnnaJack H. Mendelson

Affiliated Societies

American Psychiatric AssociationAmerican Society for Pharmacology and Experimental

TherapeuticsAmerican Society for Clinical Pharmacology and Therapeu-

ticsAmerican College of Neuropsychopharmacology


18/36

200

During the next several years, the NationalMedical A ssociation, the Society for BehavioralMedicine, the American Chemical Society, theAmerican Sociological Association, the Ameri-can Medical Association and the American

Psychological Association also became affili-ated with the CPDD, Inc. At the present time,all of these scientific organizations except theAmerican Sociological Association continue assponsors of the independent Committee. Eachof the affiliated societies appointed a represen-tative to an enlarged Board of Directors.

Dr. E. Leong Way was elected as Chairmanof the Board of Directors in 1978, replacing Dr.Hollister who had officially retired as a memberof the CPDD, Inc. Dr. Keith F. Killam waselected as the Secretary and Treasurer of theBoard. Dr. Hollister returned to the Committeeas the Executive Secretary of the corporationin July, 1979, replacing Dr. Harwood. Themembers of the CPDD and the affiliated soci-eties, from 1977 to the present are listed inTables VI to XVIII. The Tables reflect themembership at the time of the Annual Meetingfor the denoted year.

Table VII. Members of the Executive Committee and theBoard of Directors of the CPDD, Inc., in 1978.

Daniel X. Freedman, ChairmanTheresa Harwood, Executive SecretaryJoseph Cochin Jack H. MendelsonLouis S. Harris John ODonnellArthur E. Jacobson Beny J. PrimmJerome H. Jaffe Herbert A. RaskinDonald R. Jasinski Lee N. RobinsArthur S. Keats Travis ThompsonEverette L. May

Board of DirectorsDaniel X. Freedman, American Psychiatric AssociationLeo E. Hollister, American Society for Clinical Pharmacol-

ogy and TherapeuticsKeith F. Killam, American College of Neuropsycho-

pharmacologyEverette L. May, American Chemical SocietyHerbert A. Raskin, American Medical AssociationE. Leong Way, American Society for Pharmacology and

Experimental Therapeutics

Table VIII. Members of the Executive Committee andthe Board of Directors of the CPDD, Inc., in 1979.

Joseph Cochin, ChairmanLeo E. Hollister, Executive SecretaryJoseph V. Brady Arthur S. KeatsTroy Duster Harold KalantCharles W. Gorodetzky Everette L. MayLouis S. Harris Jack H. MendelsonTheresa Harwood John ODonnellArthur E. Jacobson Charles R. SchusterJerome H. Jaffe Henry H. Swain

Board of Directors

E. Leong Way, Chairman, American Society for Pharmacol-ogy and Experimental Therapeutics

Daniel X. Freedman, American Psychiatric AssociationKeith F. Killam, American College of Neuropsycho-

pharmacologyEverette L. May, American Chemical SocietyEdward C. Senay, American Medical AssociationBeny J. Primm, National Medical AssociationJames A. Woods, American Psychological AssociationRaymond W. Houde, American Society for Clinical Pharma-

cology and Therapeutics

Table IX. Members of the Executive Committee and theBoard of Directors of the CPDD, Inc., in 1980.

Joseph Cochin, ChairmanLeo E. Hollister, Executive SecretaryJoseph V. Brady Arthur S. KeatsTroy Duster Harold KalantCharles W. Gorodetzky Everette L. MayLouis S. Harris Jack H. MendelsonTheresa Harwood Charles R. SchusterArthur E. Jacobson Henry H. SwainJerome H. Jaffe

Board of Directors

E. Leong Way, Chairman, American Society for Pharmacol-

ogy and Experimental TherapeuticsDaniel X. Freedman, American Psychiatric AssociationKeith F. Killam, American College of Neuropsycho-

pharmacologyEverette L. May, American Chemical SocietyEdward C. Senay, American Medical AssociationBeny J. Primm, National Medical AssociationJames A. Woods, American Psychological AssociationRaymond W. Houde, American Society for Clinical Pharma-

cology and Therapeutics


19/36

201

Table X. Members of the Executive Committee and theBoard of Directors and Permanent Liasion of the CPDD,Inc., in 1981.

Joseph Cochin, ChairmanLeo E. Hollister, Executive Secretary

Joseph V. Brady Arthur S. KeatsTroy Duster Harold KalantCharles W. Gorodetzky Everette L. MayLouis S. Harris Jack H. MendelsonTheresa Harwood Charles R. SchusterArthur E. Jacobson Henry H. SwainJerome H. Jaffe

Board of DirectorsE. Leong Way, Chairman, American Society for Pharmacol-

ogy and Experimental TherapeuticsRaymond W. Houde, American Society for Clinical Pharma-

cology and TherapeuticsDaniel X. Freedman, American Psychiatric AssociationKeith F. Killam, American College of Neuropsycho-

pharmacologyEverette L. May, American Chemical SocietyEdward C. Senay, American Medical AssociationBeny J. Primm, National Medical AssociationJames A. Woods, American Psychological Association

Pemanent LiaisonLouis S. HarrisArthur E. Jacobson

Table XI. Members of the Executive Committee and theBoard of Directors and Permanent Liaison of the CPDD,Inc., in 1982.

Joseph V. Brady, ChairmanJoseph Cochin, Executive Secretary

Martin W. Adler Theresa HarwoodSidney Archer Leo E. HollisterWilliam T. Beaver Jerome H. JaffeRichard J. Bonnie Harold KalantTheodore J. Cicero Charles P. OBrienTroy Duster Charles R. SchusterCharles W. Gorodetzky Henry H. Swain

BoaTd of DirectorsE. Leong Way, Chairman, American Society for Pharmacol-

ogy and Experimental TherapeuticsRaymond W. Houde, American Society for Clinical Pharma-

cology and TherapeuticsKeith F. Killam. American College of Neuropsycho-

pharmacologyEverette L. May, American Chemical SocietyJack H. Mendelson, American Psychiatric AssociationBeny J. Primm, National Medical AssociationLee N. Robins, American Sociological AssociationEdward C. Senay, American Medical AssociationJames A. Woods, American Psychological Association

Permanent LiaisonLouis S. HarrisArthur E. Jacobson

In order to gather scientists representingthe diverse scientific disciplines encompassedby the CPDDs continued emphasis on physicaldependence potential and abuse liability, andits attempt to realize its goals and purposes,the Executive Committee continued to expandits membership, reaching a plateau of 18 votingmembers by 1987. Although scientists electedto the Executive Committee had been limited toa 3-year term under the auspices of the NAS,the Incorporated Committee, in principle,increased the term to four years and consecu-tive election to a second term was barred.

At its inception in 1977, the members of theBoard of Directors were limited to a 5-yearterm of office. The ability of the sponsoringorganization to reappoint its representative toconsecutive terms was, initially, unlimited.Acceptance of the representative suggested bythe affiliated society to the Board of Directors

of the CPDD was, however, the prerogative ofthe Executive Committee.

In the beginning, the Board of Directors andthe Executive Committee of CPDD, Inc., wereassigned different roles. The Board of Directorshad the responsibility of guiding the ExecutiveCommittee and suggesting new endeavors,while the Executive Committee was the imple-menting arm of the organization. Thisseparation in roles essentially disappearedover the following decade as will he describedbelow and the by-laws of the CPDD were modi-fied in 1987 to reflect the fact that, whetherappointed or elected, individuals were function-ally equivalent in their work on the Committee.

The Incorporated Committee continued thepolicy of holding two meetings a year, aninterim meeting in December and a secondmeeting in conjunction with the Annual Scien-


20/36

202

Table XII. Members of the Executive Committee and theBoard of Directors of the CPDD, Inc., in 1983.

Leo E. Hollister, ChairmanJoseph Cochin, Executive SecretaryMartin W. Adler Lloyd D. Johnston

Sidney Archer Mary Jeanne KreekWilliam T. Beaver William R. MartinRichard J. Bonnie Roger E. MeyerTheodore J. Cicero Charles P. OBrienMarian W. Fischman Akira E. TakemoriRoland R. Griffiths Julian E. VillarrealDonald R. Jasinski

Board of DirectorsBeny J. Primm, Chairman, National Medical AssociationJoseph V. Brady, Society of Behavioral MedicineRaymond W. Houde, American Society for Clinical Pharma-

cology and TherapeuticsKeith F. Killam, American College of Neuropsycho-

pharmacologyEverette L. May, American Chemical SocietyJack H. Mendelson, American Psychiatric AssociationLee N. Robins, American Sociological AssociationEdward C. Senay, American Medical AssociationE. Leong Way, American Society for Pharmacology and

Experimental TherapeuticsJames A. Woods, American Psychological Association

Table XIII. Members of the Executive Committee andthe Board of Directors of the CPDD, Inc., in 1984.

Leo E. Hollister, ChairmanJoseph Cochin, Executive SecretaryMartin W. Adler Donald R. JasinskiSidney Archer Lloyd D. JohnstonWilliam T. Beaver Mary Jeanne KreekRichard J. Bonnie William R. MartinTheodore J. Cicero Roger E. MeyerWilliam L. Dewey Charles P. OBrienMarian W. Fischman Akira E. TakemoriRoland R. Griffiths

Board of Directors

Beny J. Primm, Chairman, National Medical AssociationJoseph V. Brady, Society of Behavioral MedicineRaymond W. Houde. American Society for Clinical Pharma-




Table XIV. Members of the Executive Committee and theBoard of Directors of the CPDD, Inc., in 1985.

Theodore J. Cicero, ChairmanJoseph &chin, Executive SecretaryMartin W. Adler Lloyd D. Johnston

Thomas F. Burks John KaplanWilliam L. Dewey Conan KornetskyLoretta P. Finnegan Mary Jeanne KreekMarian W. Fischman William R. MartinRoland R. Griffiths Roger E. MeyerLeo E. Hollister Akira E. TakemoriDonald R. Jasinski

Board of Directors

Beny J. Primm, Chairman, National Medical AssociationJoseph V. Brady, Society of Behavioral MedicineRaymond W. Houde, American Society for Clinical Pharma-




Table XV. Members of the Executive Committee and theBoard of Directors of the CPDD, Inc., in 1986.

Mary Jeanne Kreek, ChairmanTheodore J. Cicero, Past ChairmanWilliam L. Dewey, Chairman-ElectJoseph Cochin (deceased), Executive SecretaryMartin W. Adler Donald R. JasinskiThomas F. Burks Lloyd D. JohnstonRichard A. Deitrich John KaplanLoretta P. Finnegan Conan KornetskyMarian W. Fischman Horace H. LohRoland R. Griffiths Akira E. TakemoriLeo E. Hollister

Board of Directors

Beny J. Primm, Chairman, National Medical AssociationJoseph V. Brady, Society of Behavioral MedicineRaymond W. Houde, American Society for Clinical Pharma-


pharmacologyEverette L. May, American Chemical SocietyJack H. Mendelson, American Psychiatric AssociationE. Leong Way, American Society for Pharmacology and



21/36

203

Table XVI. Members of the Executive Committee and theBoard of Directors of the CPDD, Inc., in 1987.

Mary Jeanne Kreek, ChairmanTheodore J. Cicero, Past ChairmanWilliam L. Dewey, Chairman-Elect

Martin W. Adler, Executive SecretaryMitchell B. Balter John KaplanWilliam T. Beaver Sheppard G. KellamThomas F. Burks Herbert D. KleberRichard A. Deitrich Conan KornetskyLoretta P. Finnegan Horace H. LohMarian W. Fischman Edward C. SenayRoland R. Griffiths Akira E. TakemoriDonald R. Jasinski

Board of Directors

Keith F. Killam, Chairman, American Society for Pharma-cology and Experimental Therapeutics

James A. Woods, Secretary-Treasurer, American Psychol-ogical Association

Joseph V. Brady, Society of Behavioral MedicineKathleen M. Foley, American Society for Clinical Pharma-

cology and TherapeuticsEverette L. May, American Chemical SocietyJack H. Mendelson, American Psychiatric AssociationBeny J. Primm, National Medical AssociationE. Leong Way, American College of Neuropsycho-

pharmacology

Table XVII. Members of the Board of the CPDD, Inc., andaffiliated societies in 1988.

William L. Dewey, ChairmanThomas F. Burks, Chairman-ElectMary Jeanne Kreek. Past Chairman

Joseph V. Brady, Secretary/TreasurerKeith F. Killam, Chairman, Advisory CouncilMartin W. Adler, Executive SecretaryRobert L. Balster Herbert D. KleberMitchell B. Balter Conan KornetskyWilliam T. Beaver Horace H. LohRichard A. Deitrich Everette L. MayLoretta P. Finnegan Donald E. McMillanKathleen M. Foley Nancy K. MelloLouis S. Harris Jack H. MendelsonReese T. Jones Beny J. PrimmJohn Kaplan Edward C. SenaySheppard G. Kellam E. Leong Way

Affiliated Societies

American Chemical SocietyAmerican College of NeuropsychopharmacologyAmerican Psychiatric AssociationAmerican Psychological AssociationAmerican Society for Clinical Pharmacology and Therapeu-

ticsAmerican Society for Pharmacology and Experimental

TherapeuticsNational Medical AssociationSociety of Behavioral Medicine

tific Meeting in the Spring or early Summer. Inorder to facilitate the decision-making processof the Committee on a daily basis, an executiveworking group, or Action Committee, was for-mally constituted at an interim meeting in 1979.The President and the Executive Secretary ofthe Corporation, and the Chairman of the Exec-utive Committee, became the members of theAction Committee at that time. With the revi-sion of the by-laws in 1985 (under the guidanceof a very active Rules Committee, with Dr.Charles Gorodetzky as Chairman of that stand-ing subcommittee1 the Chairman, Chairman-elect and Past-chairman of the ExecutiveCommittee, the Secretary/Treasurer and theChairman of the Board of Directors (later, theAdvisory Council) and the Executive Secretaryof the Corporation became the constituents ofthe Action Committee. In 1985, the member-ship of the Corporation was restated as beingonly those individuals who were members of

Retired from Board in April, 1988. Replaced by Donald R.

Jasinski.

the then Board of Directors (who were, now, tobe appointed to a 4-year term by the affiliatedsocieties with the concurrence of themembership of the Corporation), and the mem-bers of the Executive Committee, who contin-ued to be elected to a I-year term. Thisdefinition clarified the positions of subcommit-tee chairmen, some of whom were not membersof either the Executive Committee or theBoard of Directors, and the status of the Execu-tive Secretary of the Corporation which, in1986, became a salaried position. Thesesubcommittee chairmen and the ExecutiveSecretary of the Corporation were not, then,voting members of the Corporation. The officesformerly titled Chairman of the Board of Direc-tors and President of the Corporation werecombined, and the positions of Chairman of the


22/36

204

Table XVIII. Members of the Board of the CPDD, Inc.,and affiliated societies in 1989.

William L. Dewey, ChairmanThomas F. Burks, Chairman-ElectMary Jeanne Kreek, Past Chairman

Joseph V. Brady, SecretaryfIreasurerKeith F. Killam, Chairman, Advisory CouncilMartin W. Adler, Executive SecretaryRobert L. Balster James M. KulikowskiMitchell B. Balter Horace H. LohWilliam T. Beaver Donald E. McMillanThomas J. Crowley Nancy K. MelloRichard A. Deitrich Jack H. MendelsonLoretta P. Finnegan Beny J. PrimmLouis S. Harris Kenner C. RiceDonald R. Jasinski Edward C. SenayReese T. Jones Eric J. SimonSheppard G. Kellam E. Leong WayHerbert D. Kleber

Affiliated SocietiesAmerican Chemical SocietyAmerican College of NeuropsychopharmacologyAmerican Psychiatric AssociationAmerican Psychological AssociationAmerican Society for Clinical Pharmacology and Therapeu-

ticsAmerican Society for Pharmacology and Experimental

TherapeuticsNational Medical AssociationSociety of Behavioral Medicine

Table XIX. Standing Committees and Liaison members ofthe Committee on Problems of Drug Dependence, Inc., in1983.

Committee ChairmenCharles W. Gorodetzky, RulesLouis S. Harris, Scientific MeetingsArthur E. Jacobson, Drug Testing Program

Permanent LiaisonJerome H. Jaffe, Veterans AdministrationHoward McClain, Drug Enforcement AdministrationHeinz Sorer, National Institute on Drug AbuseEdward C. Tocus, Food and Drug Administration

Table XX. Standing Committees and Liaison members ofthe Committee on Problems of Drug Dependence, Inc., in1984 and 1986.

Committee ChaivmenCharles W. Gorodetzky, Rules

Louis S. Harris, Scientific MeetingsArthur E. Jacobson, Drug Testing Program

Permanent LiuieonHarold Kalant, Addiction Research Foundation (Toronto)Howard McClain, Drug Enforcement AdministrationHeinz Sorer, National Institute on Drug AbuseEdward C. Tocus, Food and Drug Administration

Table XXI. Standing Committees and Liaison members ofthe Committee on Problems of Drug Dependence, Inc., in1986.

Committee ChairmenCharles W. Gorodetzky, RulesLouis S. Harris, Scientific MeetingsArthur E. Jacobson, Drug Testing Program

Permanent LiuiwnJerome H. Jaffe, National Institute on Drug AbuseHarold Kalant, Addiction Research Foundation (Toronto)Howard McClain, Drug Enforcement AdministrationCharles P. OBrien, Veterans AdministrationBoris Tabakoff, National Institute on Alcohol Abuse and

AlcoholismEdward C. Tocus, Food and Drug Administration

Table XXII. Standing Committees and Liaison membersof the Committee on Problems of Drug Dependence, Inc., in1987.

Committee ChairmenTheodore J. Cicero, Animal Testing CommitteeMarian W. Fischman, Human TestingCharles W. Gorodetzky, Rules

Louis S. Harris, Scientific MeetingsArthur E. Jacobson, Drug Testing Program

Permanent LiaisonHarold Kalant, Addiction Research Foundation (Toronto)Howard McClain, Drug Enforcement AdministrationCharles R. Schuster, National Institute on Drug AbuseBoris Tabakoff, National Institute on Alcohol Abuse and

AlcoholismEdward C. Tocus, Food and Drug Administration


23/36

Table XXIII. Standing Committees and Liaison membersof the Committee on Problems of Drug Dependence, Inc., in1988 and 1989.

Committee ChairmenTheodore J. Cicero, Animal Testing Committee

Marian W. Fischman, Human TestingCharles W. Gorodetzky, RulesLouis S. Harris, Scientific MeetingsArthur E. Jacobson, Drug Testing Program

Permanent LiaisonHarold Kalant, Addiction Research Foundation (Toronto)Howard McClain, Drug Enforcement AdministrationCharles R. Schuster, National Institute on Drug AbuseBoris Tabakoff, National Institute on Alcohol Abuse and

AlcoholismFrancis J. Vocci, Food and Drug Administration

Executive Committee, Past-chairman, andChairman-elect were clarified with this revisionof the by-laws. As a result of these modifica-tions, in 1985 a 16-member ExecutiveCommittee was defined, with the Past-chair-man as a 17th member. Two appointed mem-bers of the Board of Directors served as voting

205

members of the Executive Committee in theCorporation, to legitimize the corporate struc-ture of the organization according to the laws ofthe District of Columbia, where the CPDDincorporated. During that meeting in 1985, it

was decided to limit the term of all subcommit-tees to 1 year. A further change in the struc-ture of the Committee was initi

may article

Documents