An evaluation of narcotics controls discloses that our Nation's statutes are not sufficiently flexible in view of new discoveries in syn¬ thetic . Suggested changes include a redefinition of addic¬ tion and uniform national and international laws. Liability and Narcotics Control

NATHAN B. EDDY, M.D., and HARRIS ISBELL, M.D.

AMONG the most effective measures for the pert Committee on Addiction-Producing __fjLprevention of addiction are the Fed¬ of the World Health Organization drafted a eral laws and international treaties controlling definition of addiction (_?). The committee the production and distribution of the drugs of said, "Drug addiction is a state of periodic or addiction and the source materials from which chronic intoxication, detrimental to the indi¬ these drugs are derived. The application and vidual and to society, produced by the repeated administration of these laws have steadily be¬ consumption of a drug (natural or synthetic). come more complex. A large number of syn¬ Its characteristics include: (1) an overpowering thetic drugs with pharmacological effects and desire or need (compulsion) to continue taking addiction liability similar to that of the drug and to obtain it by any means; (2) a have been discovered and have created some tendency to increase the dose; (3) a psychic difficult problems of classification and control. (psychological) and sometimes a physical de¬ It is now also known that substances, such as pendence on the effects of the drug." the and the , cov¬ In its third report (#) in 1952, the expert ered by the food and drug but not by the nar¬ committee wrote an explanation of the charac¬ cotic laws, are susceptible to abuse and may teristics of addiction designed particularly to produce a different addiction from that caused express its view on a distinction between addic¬ by the . It is the purpose of this paper tion and habituation. In 1957, to clarify to review the historical origin of the present further this distinction, the expert committee narcotic laws and to discuss changes in them reworded its definition of addiction without which seem desirable in the light of recent material change in its meaning (3). knowledge. This definition received some acceptance but also much criticism. It was not meant to be Definition of Addiction pharmacological, nor strictly speaking scien¬ tific, but practical, and was intended to include In 1950, at the request of the Commission on the diverse substances currently under interna¬ Narcotic Drugs of the United Nations, the Ex- tional narcotics control. State and national narcotics laws and regulations and international Dr. Eddy is chief, Section on Analgesics, National narcotics conventions are designed to prevent or Institute of Arthritis and Metabolic Diseases, and at least limit abuse of cocaine and marihuana Dr. Isbett is director, Addiction Research Center, as well as of opium and the potent analgesics. National Institute of Mental Health, Public Health Though all of these substances are commonly Service. * and loosely termed narcotics, their properties Vol. 74, No. 9, September 1959 755 differ so widely that they are similar only in be¬ Export Act, an extensive revision of the act of ing subject to abuse and in creating social 1909 authorizing the importation of such quan¬ dangers. Of necessity, any definition attempt¬ tities only of opium and coca leaves as were ing to cover all of them had to be very broad. found to be necessary for medical and legitimate needs. Importation of any form of narcotic National Control drug except crude opium and coca leaves was prohibited. Exportation of manufactured When control was first considered (1909- drugs was permitted under a system of control 12) and for a considerable time thereafter, designed to assure their use for medical needs only cocaine and opium and its alkaloids were only in the country of designation. taken into account. Their abusive use was rec¬ June 7, 1924- Amendment to the Narcotic ognized and considered of sufficient importance Drugs Import and Export Act prohibiting the to warrant strict control, even at the expense of importation of opium for the manufacture of placing a burden upon drug manufacturers, heroin. pharmacists, and physicians, as well as upon the June 14, 1930. An act establishing the Bu¬ which had to the con¬ government implement reau of Narcotics in the Department of the trol. Relatively few individuals abused both Treasury. opiates and cocaine, the effects of which are August 2, 1937. The Marihuana Tax Act- different and in some respects opposite; yet Imposition of registration and occupational tax both were called narcotics and both were sub¬ on all persons who produced, imported, manu¬ to the same control measures. jected factured, sold, or transferred marihuana. An excellent chronological review of the steps August 9, 1939. Contraband Seizure Act, in the development of national and interna¬ authorizing confiscation of any vessel, vehicle, tional control of narcotic drugs was published or aircraft used to facilitate transportation and in 1953 (4). so forth of contraband narcotics or marihuana. Merely listing the principal acts of Congress December 11, 191$. Opium Poppy Control on this subject with their chief intent will indi¬ Act, prohibiting the growth of the opium cate the progress of events and the development poppy in the United States, except under of thought on the problem of control: special license issuable when need is shown for February 9, 1909. Prohibition of importa¬ domestic production for medical and scientific tion of opium and its preparations and deriva¬ uses. tives except for medicinal purposes and abso¬ July 1,1944- A statute making the Federal lute prohibition of importation of smoking narcotic laws applicable to pethidine (meperi¬ opium. dine, Demerol) under the statutory designation January 17, 191^. Prohibition against ex¬ "Isonipecaine." portation of opium and cocaine and salts, and March 8,1946. The Opiates Act, or Robert¬ derivatives and preparations thereof, except to son Amendment, establishing a general proce¬ a country which regulated the entry of such dure for the expeditious application of control drugs; absolute prohibition of exportation of measures to any drug found to be dangerous smoking opium. from the addiction-liability standpoint. January 17, 1914. Prohibitive tax upon 1955-59. The Karsten bill, designed, among opium manufactured for smoking purposes. other things, to implement our obligation under December 17,1911^. Harrison Narcotic Law, the 1948 protocol to bring new substances un¬ an internal revenue measure by tax and regis¬ der narcotics control. This bill is still pending. tration limiting the availability of narcotic Consideration is being given to its possible drugs to medical and scientific uses, and regu¬ amendment looking to greater flexibility in our lating production, manufacture, and distribu¬ system of narcotics control, tailoring, so to tion, through channels of medical supply to the speak, the degree of control to the degree of dispensing registrants, the qualified practi¬ risk to public health. Among those giving tioner, and druggist. thought to the desirability of such amendment, May 26, 1922. Narcotic Drugs Import and the Committee on Drug Addiction and Narcot-

756 Public Health Reports ics of the National Research Council discussed and scientific requirements. Thereafter, each the problem at length at its 20th meeting, Jan¬ country was obligated to limit its manufacture uary 11,1959, and passed unanimously a resolu¬ of each of the drugs in accordance with its es¬ tion embodying its views (5). timate and to supply periodically to the Per¬ manent Central Opium Board statistics of International Control actual manufacture, consumption, importation, and exportation of those drugs. In other words, The first effective effort toward obtaining the convention contemplated the adjustment of international action to control the traffic in world manufacture to legitimate world demand, opium and the dangerous drugs obtained there¬ the control of all channels of distribution, both from was the conference of the International national and international, and provision for a Opium Commission convened in Shanghai in recording system of all narcotic drug opera¬ February 1909, on the initiative of the U.S. tions. It entrusted to international organiza¬ Government. The successive steps or agree¬ tions the task of supervising and coordinating ments on international narcotics control, again throughout the world. The convention specified reflecting the development of thought on this the drugs to be controlled and made some pro¬ problem, have progressed as follows: vision for additions to the list. International Opium Convention of 1912. Protocol of 1946. Transferred to the Com¬ Designed to bring about the gradual suppres¬ mission on Narcotic Drugs of the United Na¬ sion of the abuse of opium, morphine, and tions Economic and Social Council the functions cocaine, as also of the drugs prepared or de¬ previously carried out by the Opium Advisory rived from these substances which give rise or Committee of the League of Nations. might give rise to similar abuses. The con¬ Protocol of 1948. Established an interna¬ tracting parties agreed to enact effective laws tional procedure, analogous in principle to that or for the control of the regulations production of our Opiates Act of 1946, whereby new drugs and distribution of raw opium. A less definite found to have dangerous addiction liabilities was to smok¬ obligation imposed with respect are promptly brought under the control im¬ ing opium, and the contracting parties' best posed by the 1931 convention, the definitive efforts were to be used with to mor¬ respect finding in this case being made by the World phine and cocaine and their salts to restrict Health Organization. their import and export to authorized persons Opium Protocol of 1953. Designed to limit and to enact laws limiting exclusively to medi¬ the of to medical cal and the definitely production opium legitimate purposes manufacture, and scientific needs and to establish the areas and use of these sale, dangerous drugs. of production and sources of world supply. Geneva Narcotics Convention of 1925. In¬ This protocol has not yet become effective. tended to impose somewhat more specific obli¬ Single Convention. intended to with to control of national and Originally gations respect incorporate into a single agreement by codifi¬ international trade. It established the Perma¬ cation the provisions of the various interna¬ nent Central Board to watch continu¬ Opium tional narcotics conventions but actually un¬ ously the course of international trade in the dergoing elaboration. It is still in the drafting drugs covered by the 1912 convention, collect stage. and examine statistics, and obtain and com¬ municate to all parties explanations of appar¬ for ently excessive accumulations of the dangerous Need Flexibility drugs in any country. It is apparent that, initially, thought and ef¬ Convention of 1931. Limited the manufac¬ fort toward narcotics control were centered up¬ ture and regulated the distribution of narcotic on the crude materials, opium and coca leaves, drugs by requiring all countries, whether or not or upon the potent drugs obtained from them, parties to the convention, to supply annual morphine and its derivatives and cocaine. In estimates of their needs of stated derivatives of the United States marihuana was added to the opium and coca leaves, based solely on medical list of substances controlled because of evidence

Vol. 74, No. 9, September 1959 757 of widespread abuse. The picture changed stances which are modifications of morphine with the discovery and introduction into medi¬ whether occurring in opium or produced in cine of the first synthetic morphine-like pain- the laboratory, the 1931 convention recognized relieving drug (pethidine, meperidine, Dem- a difference and established groups I and II for erol), the tremendous impetus to research on which control regimens would be different. analgesics which followed that discovery, and Group I was further subdivided into subgroup the important advances which have been made (a) comprising morphine and similarly addict¬ in the study of addiction. It would seem de¬ ing substances, and subgroup (b) comprising sirable to consider how the picture has changed ecgonine, thebaine, and other drugs regarded as and to try to understand the implications of not themselves addicting but convertible into the change. drugs capable of producing addiction. Group Pethidine was but the first of a very large II was established to include codeine, dionin, number of substances prepared entirely by syn¬ and related substances, likewise then regarded thesis in the laboratory which exhibited in ani¬ by many as not capable of producing addiction mals and man wide differences in and but also convertible into addiction-producing properties. These sub¬ drugs. The distinction was drawn between stances also are widely different in chemical subgroup (b) and group II not on theoretical structure. Some are built upon moieties of the but on practical grounds, namely, that the morphine molecule. Others differ so greatly drugs in group II were very extensively used in chemical structure that the tentative rela¬ in medicine all over the world, whereas those in tionships of structure and analgesic action de¬ subgroup (b) were hardly used at all by the scribed by Braenden, Eddy, and Halbach (6) medical profession (8). All measures of con¬ as recently as 1955 cannot always be discerned. trol were applicable to all drugs in group I It is well recognized from clinical experience (both subgroups), but a somewhat modified and direct evaluation experiments under con¬ control was permitted for the drugs of group trolled conditions that substances derived from II. For the latter the substances themselves morphine differ in analgesic potency and addic¬ were controlled internationally in essentially tion liability and present different degrees of the same way as those in group I with only risk to public health, ranging from the great minor modifications such as greater leeway in danger of heroin, the main drug in the present- estimates of needs and other statistical matters. day illicit traffic in the United States, to rela¬ However, under the convention, compounds of tively low risk with codeine, which with proper the drugs in group II, if they were adapted to therapeutic use rarely results in addiction. normal therapeutic use, were exempted from Examples of all the synthetic chemical types international narcotics control. have been evaluated for addiction liability The U.S. laws do not recognize a distinction as well as for analgesic effect and have exhibited in the regimen of control such as that between a range of activity from much greater than group I and group II of the 1931 convention to less than In morphine substantially codeine. except insofar as specifically described prep¬ this connection the expert committee (7) has arations of not than concen¬ stated "that differ greater specified synthetic analgesic drugs tration may be sold as exempt from one another in addiction as conditionally liability just without a narcotics do derived from natural sources such as preparations prescription. drugs These limited were authorized be¬ opium; that members of each class must be con¬ exemptions sidered individually with respect to inherent fore the discovery of pethidine and the many risk and therapeutic advantage; and that the other synthetics, and the Opiates Act of 1946 made no for their extension to a risk of addiction through the use of synthetic provision drugs is neither greater nor less than the risk preparation of any synthetic. This situation encountered through the use of morphine, re¬ must be discouraging to pharmaceutical man¬ lated opium alkaloids, or substances derived ufacturers and may act as a deterrent to re¬ therefrom." search programs designed to develop analgesics For the natural alkaloids, that is, for sub¬ of low addictiveness. Since under present

758 Public Health Reports conditions any such agent could be controlled of a new substance shall be ability to produce only in the same manner as morphine, our nar¬ or sustain an addiction similar to that of mor¬ cotics laws are in a sense hampering the search phine or cocaine. If, in this connection, the for a nonaddicting pain-relieving drug. word similar is interpreted as implying Clinical experience and direct addiction ex¬ quantitative similarity, difficulty must be en¬ periments indicate that cocaine does not pro¬ countered in bringing under control a sub¬ duce physical dependence, and abrupt with¬ stance of low addiction liability, substantially drawal after prolonged use is not followed by less than that of codeine, as has been the case an abstinence syndrome. In the amounts with propoxyphene, a weak synthetic analgesic taken by addicts in the United States, however, of the group. This particular sit¬ cocaine can cause a dangerous psychosis, and uation might be clarified by making the crite¬ taken chronically it causes tachycardia, insom¬ rion for control "qualitatively similar to nia, and anorexia with resultant impairment of morphine," leaving to the judgment and ex¬ nutrition. Cocaine does produce strong psy¬ perience of the responsible authority whether chic dependence, and its prolonged use is un¬ or not the addiction liability of a particular doubtedly detrimental, hence its control by the substance is sufficient in degree to constitute a narcotics laws. Similarly, marihuana does not risk to public health and thus warrants narcotics produce physical dependence manifested by a control. It is possible that control at the man¬ withdrawal syndrome. Here, too, control is ufacturing and wholesale level only would be exercised because of the harmful effects of the adequate for substances of low addiction lia¬ drug under conditions of abuse. bility where the risk to public health is small, In recent years the Addiction Research Cen¬ leaving retail trade in drugs of minor addictive ter of the Public Health Service Hospital at potential free of narcotics control, not requir¬ Lexington, Ky., has been investigating the pos¬ ing narcotics prescriptions, narcotics records, sibility of development of physical dependence and the like. during prolonged administration of barbi¬ It has been pointed out that our narcotics turates, meprobamate, and similar drugs. It laws and regulations, while providing for has been shown conclusively that physical de¬ exempt preparations of codeine and other sub¬ pendence could develop when large doses of stances derived from morphine and even for these substances were taken chronically and preparations containing up to a certain con¬ that a characteristic abstinence syndrome fol¬ centration of morphine itself, make no provision lowed abrupt withdrawal (9-11). It was also for exempt preparations of synthetic analgesics. shown, however, that no clinically significant Since it is known that the "natural" alkaloids, degree of dependence developed in persons morphine and substances derived from it, and taking only 0.4 gram or less daily of secobarbi¬ the synthetic analgesics vary in addictiveness tal or , that is, two to four times and therefore in risk to public health, both the the usual daily oral dosage (12). It is clear "natural" and synthetic classes of drugs should from the work at Lexington that the symp¬ be treated in the same way. If exempt prepara¬ tomatology of abstinence with barbiturates or tions are safe and permissible in the "natural" meprobamate is distinctly different from class, they should be safe and permissible in abrupt withdrawal of an . Further, the synthetic class. On the other hand, if the physical dependence or addiction with barbitu¬ argument is that there is some risk in exempt rates and meprobamate has been observed in preparations of morphine and opium because clinical practice (13-15). of the possibility of abuse by the consumption It should be clear that addiction and its re¬ of multiple doses, a similar risk would be ex¬ lation to narcotics control are complex quali¬ pected with exempt preparations of synthetic tatively and quantitatively and that our substances with morphine-like addiction liabil¬ present system of control is not realistically ity. The Expert Committee on Addiction- adjusted to this complexity. The Opiates Act Producing Drugs of the World Health Organi¬ says, for example, that the criterion for control zation has pointed out repeatedly the risk of

Vol. 74, No. 9, September 1959 759 addiction through the use of multiple doses of pharmacological characteristics, might be con¬ preparations of strongly addicting substances sidered to have addiction potentiality, but con¬ (16, 17) and that admixture with other sub¬ cerning which there is no conclusive evidence stances cannot be relied upon to avoid such of such liability. The listing would make in¬ risk (18). terested parties aware that the status of such In contradistinction to what has just been said compounds would be reviewed from time to about exempt preparations of morphine, of time as experience accumulated so that if evi¬ opium, and of synthetics with comparable ad¬ dence of addiction or other abuse appeared the diction liability, a very desirable measure of proper degree of control would be applied. flexibility in narcotics control would be pro¬ To maintain the flexibility of narcotics con¬ vided by extension of the exempt preparation trol and to keep the degree of control applied provisions to substances of low addiction liabil¬ to all drugs commensurate with the degree of ity, irrespective of origin. Provided such a risk to public health, the authority designated modification does not contravene any interna¬ by law to make a finding in this field should tional agreement, the substances in pure form be empowered to revise such a finding in the would be subjected to narcotics control, but direction of either greater or less control, in¬ preparations or combinations of them, in mix¬ cluding complete removal of a substance from tures with other therapeutic non-narcotic agents narcotics control, when experience warrants from which the addicting substance would not such revision. The designated authority too be readily recoverable, would be exempt from should have for its guidance adequately repre¬ narcotics control. sentative technical advice and, before a finding Our national laws make no provision for con¬ is made, recommendations of that advisory trol of a substance not itself addicting but body should be published and an opportunity readily convertible into another substance provided for a hearing and presentation of known to be addicting. This lack could lead to additional or counter evidence by any interested grave danger, allowing free trade in the parent party, as in the 1946 Opiates Act procedure. substance and giving opportunity for clandes¬ Also it is to be understood that any revision of tine transformation into the addicting agent. It national control with respect to a particular would seem desirable to control the convertible substance must be consistent with our obliga¬ substance as one would control any substance tions under international agreements. into which it can be converted. The categories of control now provided by Addiction Redefined law or suggested herein for a realistic relation¬ ship between degree of narcotics control and Two general criteria for narcotics control are risk to health then should include: full available, "addiction-producing and addiction- public similar to control for substances having high or inter¬ sustaining (or qualitatively similar) mediate addiction liability; the oral prescrip¬ morphine," as in our 1946 Opiates Act; or "liable to the same kind of abuse and tion list of substances or mixtures having little produc¬ tive of the same kind of harmful as addiction liability; exempt status for prepara¬ effects," tions and mixtures of safe concentration from in the 1948 protocol. With either would it not be well to substitute for the heterogeneous, al¬ the standpoint of abuse; and control at the beit and wholesale level for comprehensive, definition of addiction of manufacturing only the World Health com¬ substances with low addiction Organization's expert very liability. mittee, a definition which would be specifically In addition, there would be advantage in an descriptive of the various qualitative types of official listing of certain compounds to which addiction already alluded to? The following no narcotics control is presently applied. This text is suggested: listing would include substances related to For an understanding of the need and scope those under some degree of narcotics control of narcotics control, drug addiction may be de¬ or other substances with clinical usefulness fined as a state of periodic or chronic intoxica¬ which, because of their general chemical or tion produced by the repeated consumption of

760 Public Health Reports a drug (natural or synthetic). Three qualita¬ ing to a toxic psychosis, characterized by para¬ tively different types may be recognized, the noid delusions. characteristics of which are: Marihuana (), like cocaine, produces Opiate addiction, of which morphine addic¬ emotional (psychic or psychological) depend¬ tion is the prototype, has three major compo¬ ence only. Physical dependence does not de¬ nents: tolerance, physical dependence, and velop and there is no abstinence syndrome. emotional (psychic or psychological) depend¬ Also little, if any, tolerance develops. Abuse ence. Tolerance, the need for an increasing dose is often sporadic, consisting of a periodic in¬ to produce an effect, is an inevitable accom¬ toxication characterized by elation and distor¬ paniment of opiate addiction but does not de¬ tion of time and space perception. velop equally to all effects nor necessarily The amphetamines (benzedrine, ^-ampheta¬ parallel to physical dependence. Physical de¬ mine) also produce only emotional dependence. pendence is an altered physiological state which There is no physical dependence, no abstinence requires continued administration of a drug to syndrome, and very little tolerance. Chronic prevent the appearance of a characteristic ill¬ intoxication resulting from abuse resembles in ness, termed an abstinence syndrome. Emo¬ symptomatology chronic intoxication with co¬ tional dependence is substitution of the use caine. of the drug for other adaptive behavior, the addiction is characterized by use of the drug becoming the answer to all of emotional (psychic or psychological) depend¬ life's problems. The abstinence syndrome is a ence, physical dependence, and partial toler¬ self-limited illness, beginning with yawning, ance, but it implies habitual consumption of perspiration, rhinorrhea, and lacrimation, amounts far in excess of usual therapeutic doses. progressing to dilatation of the pupil, waves While barbiturate addiction has the same three of gooseflesh, twitching of various muscle components as opiate addiction, there are two groups, hot and cold flashes, and restlessness significant differences. First, with the opiates which may become extreme. There is elevation there is evidence to indicate that physical de¬ of systolic blood pressure, respiratory rate, and pendence may begin to develop with the first rectal temperature. Retching, vomiting, and dose; with the barbiturates there is no evidence diarrhea ensue in the more severe syndromes. that significant physical dependence occurs in There is complete or almost complete anorexia patients who consume only usual therapeutic and rapid loss of weight. The time course doses. Second, the abstinence syndromes with varies: it may appear in 2 to 4 hours after the the opiates and with the barbiturates are char¬ last dose of drug and run its course in not acteristically different. The barbiturate ab¬ much more than 48 hours; it may be delayed stinence syndrome is characterized by anxiety, in onset for as much as 48 hours and persist nervousness, disturbances of cardiovascular re¬ for at least 14 days. The abstinence syndrome sponses, twitching of muscle groups, and tremor is precipitable in whole or in part when phys¬ progressing to convulsions of petit mal or ical dependence is present by the administra¬ grand mal type and confusion or both, tion of an opiate antagonist (). disorientation, and hallucinations predomi¬ Opiate addiction is always associated with a nantly visual. The abstinence syndrome, as drive or compulsion to continue taking the with the opiates, is self-limited. Some degree drug and to obtain it by any means. of compulsion to continue taking the drug will Cocaine addiction has as its chief character¬ occur in barbiturate addiction. istic emotional (psychic or psychological) de¬ Meprobamate, as well as other hypnotics, may pendence. Tolerance does not develop, there produce an addiction with the same character¬ is no physical dependence, and consequently no istics as the barbiturates. abstinence syndrome follows withdrawal of the drug. There may be a drive or compulsion to Non-Opiates and Narcotics Control continue taking the drug, depending upon the degree of psychic dependence. In some areas The consensus today, nationally and repeat¬ cocaine abuse is a periodic indulgence progress¬ edly affirmed by the Expert Committee on Ad-

Vol. 74, No. 9, September 1959 761 diction-Producing Drugs of the World Health 1. Remove any distinction between sub- Organization, is that, although abuse occurs, stances of natural or purely synthetic origin narcotics control should not be extended to the with respect to the possibility of exempt prepa- amphetamines, the barbiturates, or other seda- rations. tives. There are several reasons for this 2. Provide flexibility of narcotics control opinion. based upon the degree of risk involved, varying Clinical experience leads us to believe that from full control for substances of high ad- most persons will handle and use these drugs diction liability to control at the manufacturing as prescribed and will not develop a chronic and wholesale level only for substances of low intoxication or addiction. This is not believed addiction liability. Alternatively for the latter to be true of the opiates, cocaine, or marihuana. group, control of the pure substance and ex- Cocaine and opium are derived from plants emption from control of its preparations witl whose production is limited to certain areas of other therapeutic agents might be provided. the world from which they are transported to 3. Bring, local regulations into line with the processing and consuming countries. Interna- international narcotics conventions. tional control is absolutely necessary. Am- 4. Encourage the development of much phetamines, barbiturates, and other hypnotics needed analgesics of an efficacy more or less are produced primarily by local manufactur- comparable to codeine which might have low ers, making control of imports and exports less addiction liability by making possible a com- of a problem and control of these drugs by local mensurate degree of narcotics control. measures effective. Furthermore, indications 5. Clarify the meaning of addiction in rela- for the medical use of the amphetamines or of tion to narcotics control, by descriptive defini- the hypnotics are more numerous and far tion and by basing the application of control to broader than indications for the opiates, co- new substances upon properties qualitatively caine, or marihuana. The barbiturates are similar to those of morphine. widely used in the treatment of epilepsy, peptic ulcer, hypertension, mild neuroses, and simple REFERENCES insomnia. Meprobamate is finding wide appli- (1) World Health Organization, Expert Committee cation in mental disease. The amphetamines on Drugs Liable to Produce Addiction: Report are used medically as anorexic agents, for the on the second session, 190. Technical Report treatment of narcolepsy, to elevate mood in de- Series No. 21. Geneva, March 1950, p. 6. pressed individuals, to elevate blood pressure (2) World Health Organization, Expert Committee on Drugs Liable to Produce Addiction: Third in shock, and in many other situations. report. Technical Report Series No. 57. On the other hand, the main indication for Geneva, 1952, p. 9. use of opiates is the presence of severe pain; the (3) World Health Organization, Expert Committee use of cocaine is practically limited to local an- on Drugs Liable to Produce Addiction: Seventh esthesia; and marihuana has no medical indi- report. Technical Report Series No. 116. Geneva, 1957, p. 9. cation. To place the restrictive regulations of (4) Tennyson, A. L.: History and mechanism of in- narcotic laws on the amphetamines, the bar- ternational and national control of drugs .of biturates, and other sedatives would hamper addiction. Am. J. Med. 14: 578-585, May 1953. proper medical use and would not be justified (5) National Academy of Sciences-National Research in view of the relatively low public health risk Council, Committee on Drug Addiction and Narcotics: Minutes of twentieth meeting, 10-11 which is already mitigated through regulations January 1959. Washington, D.C., p. 2117. in respect to these drugs in the food and drug (6) Braenden, 0. J., Eddy, N. B., and Halbach, H.: statutes, both Federal and State. Synthetic substances with morphine-like effect; Relationship between chemical structure and Conclusions analgesic action. Bull. World Health Org. 13: It is concluded that implementation of sug- 937-998 (1955). (7) World Health Organization, Expert Committee gestions made in the discussion with respect to on Drugs Liable to Produce Addiction: Sixth changes in our national narcotics control report. Technical Report Series No. 102. regimen would: Geneva, 1956, p. 5.

762 Public Health Reports (8) League of Nations: Historical and technical (14) Lemere, F.: Habit-forming properties of mepro- study of convention for limiting the manufac- bamate. A.M.A. Arch. Neurol. & Psychiat. 76: ture and regulating the distribution of narcotic 205-206, August 1956. drugs of J 13, 1931. 1937, pp. 29-30. (15) Ewing, J. A., and Haizlip, T. M.: A controlled (9) Isbell, H., et al.: Chronic barbiturate intoxica- study of the habit-forming propensities of me- tion. A.M.A. Arch. Neurol. & Psychiat. 64: 1- probamate. Am. J. Psychiat. 114: 835, March 28, July 1950. 1958. (10) Fraser, H. F., et al.: Chronic barbiturate intoxi- (16) World Health Organization, Expert Committee cation: Further studies. A.M.A. Arch. Int. on Habit-Forming Drugs: Report on the first Med. 94: 34-41, July 1954. session, held 24-29 Jan. 1949. In Official rec- (11) Essig, C. F.: Withdrawal convulsions in dogs ords of the World Health Organization, No. 19. following chronic meprobamate intoxication. Geneva, 1949, pp. 29-34. A.M.A. Arch. Neurol. & Psychiat. 80:414-417, (17) October 1958. World Health Organization, Expert Committee (12) Fraser, H. F., et al.: Degree of physical de- on Addiction-Producing Drugs: Ninth report. pendence induced by or pentobar- Technical Report Series No. 160. Geneva, 1959, bital. J.A.M.A. 166: 126-129, Jan. 11, 1958. p. 7. (13) Kalinowsky, L. B.: Convulsions in nonepileptic (18) World Health Organization, Expert Committee patients on withdrawal of barbiturates, alco- on Drugs Liable to Produce Addiction. Fifth hol, and other drugs. A.M.A. Arch. Neurol. & report. Technical Report Series No. 95. Psychiat. 48: 946-956, December 1942. Geneva, March 1955, p. 8.

Training in Epidemiology A course in applied epidemiology will be offered at the Rocky Mountain Field Training Station of the Communicable Disease Cen- ter, Public Health Service, in Denver, Colo., November 16-20,1959. Designed primarily for physicians who investigate disease out- breaks or who have administrative responsibility for such investi- gations, this course serves as a review for experienced health administrators and as a guide to physicians new to public health. Emphasis is placed on developing an understanding of the use of epidemiological techniques to solve problems pertaining to prevent- able diseases. Lecture-discussion sessions and audiovisual aids are used in the presentations. Group participation is stressed through group solution of epidemiological problems, seminars, and panel dis- cussions. Registrants will be expected to attend all sessions of the course. Further information and application forms may be obtained from: Chief, Communicable Disease Center, Public Health Service, 50 Seventh Street NE., Atlanta 23, Ga., Attention: Chief, Training Branch; or from: Public Health Service, Region VIII, First National Bank Building, Denver 2, Colo.

Vol. 74, No. 9, September 1959 763