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J. VW. Res.,Vol.24.Suppl.2, pp. 135444,1990. Pnntedin Great Britain.

THE BENZODIAZEPINES

AS DRUGS OF ABUSE

JONATHAN 0. COLE*and ROBERTJ. CHIARELLO? *Department of Psychopharmacology, McLean Hospital, Belmont, Massachusetts, and the tNational Institute on Drug Abuse, Rockville, Maryland, U.S.A. Summary-Benzodiazepines are rarely used as “party” or “good time” drugs. Recent studies of drug abuse liability have found that benzodiazepines are minor euphotiants; they are neither sought nor valued on the same level as cocaine, methaqualone, or even alcohol. Although they do have mild to moderate euphoriant effects in recreational drug users, detoxified chronic alcoholics and, at very high dosages, detoxified sedative “addicts”, only a small proportion of patients entering drug abuse treatment programs cite benzodiazepine use as their primary drug problem. However, it is difficult to estimate the extent to which benzodiazepines are primary drugs of abuse, i.e. the extent of their ability to induce euphoria with psychic dependence and active drug-seeking behavior. This may be due in part to inconsistent or ambiguous reporting terminology and reliance on laboratory studies without comparisons with actual street use. In addition, it is unclear if patients admitted to emergency rooms for non-medical use of benzodiazepines are typical of all patients who abuse these drugs. This article will examine the current data available on benzodiazepine abuse. and will assess the extent to which benzodiazepines are used as primary dtugs of abuse.

INTRODUCTION SINCE the late 196Os, the benzodiazepines have consistently been among the most commonly prescribed medications in the United States. The major reasons for this are these agents are highly effective for a number of common medical straightforward: disorders and generally are quite safe, particularly in comparison to the class of drugs they have extensively replaced, the barbiturates. Recently, however, there has been a good deal of alarm about their misuse in the popular media and in some professional circles. Despite these developments, there is surprisingly inadequate meaningful clinical and descriptive data for the benzodiazepines on use am3 misuse by patients, on inappropriate prescribing practices by doctors in the various specialties, and on the outright abuse by persons with serious substance abuse disorders seeking a euphoric experience. The information available is in two major forms: numerical but superficial survey, emergency room, or treatment program data, which pose major problems in interpretation, and which provide little or no useful clinical context, and laboratory studies. The available national survey data are difficult to interpret because all the frequency figures relate to non-specific and sometimes misleading terms such as “no&medical use” and “tranquilizers”, and the statistical detail one wants for specific substances and specific kinds of users usually is not there. “Non-medical use” usually is interpreted by the respondent and would encompass all instances wherein the benzodiazepine or other sedative was not prescribed for the individual. This would include the person who borrows a friend’s

Address correspondence to Jonathan 0. Cole, M.D., Chief, Psychopharmacology,McLean Hospital, 115Mill Street, Belmont, MA 02178, U.S.A. 135

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or a family member’s benzodiazepine during a period of marked stress (e.g. death of a spouse or child), for anxiety or insomnia, as well as the street user who illicitly obtains the drug to induce euphoria. The adjunctive use of a benzodiazepine to alleviate the jitteriness of cocaine or amphetamine abuse would also not be separated out under this broad “nonmedical” rubric. The laboratory studies are of reinforcement properties as gauged by self-administration paradigms in animals and humans, as well as of the subjective effects of, or drug preferences for, benzodiazepines in usually normal volunteers. All of those studies are intended to serve as indirect measures of abuse liability. Only one study by GRIFFITHS et al. (1984), comparing diazepam and oxazepam, makes any significant effort to obtain pertinent data on the comparative illicit use frequencies of the two drugs. Our interest focuses chiefly on the extent to which benzodiazepines are primary drugs of abuse in the sense that they are taken to induce euphoria and result in dependency and active drug-seeking behavior. This concept specifically excludes patients who appropriately take moderate to high benzodiazepine doses for months or years for psychiatric or medical symptoms and become physically dependent. This restrictive approach parallels the one commonly taken in the field of narcotic use, wherein street users of heroin are clearly a different group, and represent a much graver problem than medical patients with legitimate chronic pain syndromes, often related to cancer, who become dependent on drugs. There is also an uncertain gray zone here because, as in the case with patients dependent on medically prescribed opiates, some patients taking prescribed benzodiazepines may increase their intake beyond that intended or sanctioned by their physician (JUERGENSet al., 1988). This paper is by no means comprehensive but rather seeks to outline the basic architecture of the problem. THE VIEW FROM MCLEANHOSPITAL McLean Hospital is a large, suburban, private psychiatric facility with 325 beds and more than 1500 admissions a year. A total of 25 beds are reserved for patients with primary substance abuse problems. All patients have health insurance or pay with private funds. As chief of the psychopharmacology consultation service, the senior author gets a fairly comprehensive view of how such active medications are prescribed and used by patients. In this setting, patients with primary intense benzodiazepine abuse are quite rare. In the last year, one patient claimed to be taking 10 mg of alprazolam several times a day for its euphoriant effect. He also claimed to have used diazepam in a similar way several years before. Between these periods, the patient had been treated on a number of occasions for heroin, alcohol, or PCP (phencyclidine) dependence (ALBECK, 1988). A far greater number of patients come into the hospital for benzodiazepine dependency that developed in a context of prescribed long-term treatment, usually for a pre-existing psychiatric condition. In another group of patients, benzodiazepines were taken along with alcohol, cocaine, and a variety of other drugs as a minor part of a serious poly-substance abuse pattern. Within the McLean psychopharmacology program, more than 200 college students with a

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DRUGSOFABUSE

I37

history of recreational illicit drug use volunteered for laboratory studies of the abuse liability of sedative or stimulant drugs. Screening interviews with the subjects revealed that benzodiazepines are considered minor euphoriants and are not sought or valued in the same way as cocaine, methaqualone, or even alcohol. It is our impression from this group that benzodiazepines tend to be taken when the subject wants a quiet, relaxed evening, often to relieve anxiety or tension; these agents are not used as party drugs. Cocaine, methylenedioxy methamphetamine (MDMA or “ecstasy”) or alcohol seem strongly preferred by the subjects we studied. SURVEYDATA:PRESCRII'TIONS

The two major data sources on prescriptions are the National Prescription Audit, which monitors sales of prescriptions, and the National Disease and Therapeutic Index, which surveys prescription practices of a representative sample of physicians. Both of these are conducted on an ongoing basis by IMS America, Inc. and are difficult to use and even more difficult to obtain. An excellent recent summary of these and related data sources is given by WOODS et al. (1987). Benzodiazepine prescriptions peaked at 103 million prescriptions in 1975, dropped to 67 million in 1981, and have moderately been on the increase since then. More than half of these prescriptions were written by primary care physicians other than psychiatrists, and the great majority of patients receiving them had been previously seen by their doctors. Over age 45, women users outnumber men two to one. There is no evidence in these data to suggest widespread abuse, though very little beyond diagnosis is known about why the patients need and continue to need the medication. The data do not include any estimate of the volume of benzodiazepines diverted from legal manufacturing channels or brought illegally into the United States from foreign sources. A very small number of physicians criminally prescribe large amounts of benzodiazepines (as well as other controlled substances) for profit, presumably to serious street abusers or drug dealers. Another group of physicians, also probably small in number, prescribe excessively large (or sometimes small) amounts of benzodiazepines because of poor medical knowledge, poor medical judgment, or outright carelessness. No figures are available on these kinds of illicit or inappropriate sources, and we know very little about the kinds of individuals who use medications from the corrupt “script doctors” or doctors with poor prescribing practices. SURVEYDATA:GENERALPOPULATION

Several major sources of national data, obtained for a variety of purposes, are available on rates of benzodiazepine use. One of the best and most detailed is the National Institute of Mental Health National survey of psychotherapeutic drug use among the general population, last done in 1979 (MELLINGER et al., 1981; BALTER, 1987). The interviewers asked questions about anti-anxiety drug use, showing pictures of the available drug preparations as cues. All the anti-anxiety drugs classified as such were benzodiazepines except for the uncommonly used agents meprobamate and hydroxizine. The prevalence of use by women is clearly much higher than it is for men. About 14% of

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all women versus 7.5% of men reported using a medically prescribed anti-anxiety drug in the past year. Only 1.6%, however, said they had taken such a drug daily for the whole year or longer, and only 0.6% of the total population had taken such drugs daily for 4 months to 1 year. About 2% of the sample obtained the medication from a “non-prescription” source. Of these non-prescription users, an exceedingly small number had any appreciable daily use (e.g. 0.1% showing daily use for l-4 four months, and 0% more than 4 months). This survey, as well as its predecessor carried out in 1971, has been interpreted to show that both the prescribing and the taking of the benzodiazepines are conservative, with the great majority of physicians and patients viewing their use as a short-term measure for a significant medical indication. Further information on exactly how and in what doses the respondents are using the drugs is not provided. Hence, we are essentially left with the kind of “ballpark” parameters noted above. A second survey, the National Household Survey on Drug Abuse, is conducted every few years under sponsorship of the National Institute on Drug Abuse and provides data on drug use garnered from fairly extensive interviews with a large cross section of the population (1988). Here the relevant drug class was termed “tranquilizers”, which again means chiefly benzodiazepines. “Non-medical use” was specifically assessed, but this merely excludes legitimate prescription use for a bona fide medical condition, and again does not discriminate among the several different “non-medical” ways of using the agents that were listed (e.g. taking a medication more often, or in greater amounts, or for any other reason not originally specified in the physicians’ prescription). The survey in general does not provide the kind of detail for the various substances and users that one would need to grasp the severity and magnitude of abuse. Given its limitations, it is, however, useful for demonstrating some of the gross patterns of non-medical usage. It estimates that 3.5Y0 of the sample, which translates to some 7 million people, used tranquilizers nonmedically in 1985; 1.1% used these agents in the previous month. Non-medical use occurs predominantly in persons under 35 years of age, tends to be about 1.3 times higher in males than females, and is nearly double in whites compared with blacks. A third nationally based survey is the annual High School and Young Adult Survey, which examines prevalence and trends in drug abuse for this demographic group using a representative cross section, part of which is then followed up annually thereafter (JOHNSTON et al., 1987). The survey data indicate that non-medical (i.e. “not medically supervised”) tranquilizer use has steadily declined in high school seniors since peaking in 1977. From then to 1986, lifetime prevalence has decreased from 18- 1l%, annual prevalence from 11% to 6%, and 30 day prevalence from 4.6-2.1%. The nature of this non-medical use is again unclear. The non-continuation rate for this group, which refers to individuals who have tried a drug but have not used it in the past year, has stabilized at about 50%. The 30 day prevalence of daily use is listed as 0%. We also know that 55% of recent users state they do not get “high” at all on tranquilizers. Overall, these data on young adults show a decline since the late 1970s with stabilization at a relatively modest level. Again, we do not know exactly how much and for what specific purposes these young people are using the benzodiazepines. The available indicators of severity, such as the proportion getting “high” or using regularly or classifying as “non-

BENZOIJIAZEPINES AS DRUGSOFABUSE

continuers”, tend to suggest that these generally are highly sought after and used in a major way It should be noted that the types of national sampling of individuals living in households people, and the like-subpopulations that may than those with stable living circumstances.

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are not highly preferred drugs of abuse that for their euphoriant properties. surveys discussed above are based on a and will miss itinerants, prisoners, street have much higher rates of substance abuse

PATIENT DATA COLLECTION SYSTEMS

The most prominent of the data collection systems is the Drug Abuse Warning Network (DAWN). This system, currently covering 756 emergency rooms (and 75 medical examiner’s offices) in 27 U.S. metropolitan areas, reports data on individuals who present with problems associated with nonmedical use of drugs. These data have been collected for more than ten years; the latest available data are from 1987 (National Institute on Drug Abuse, 1988). The data are of limited quality, but are properly used to provide larger trends in drug abuse and to identify new kinds of drug abuse. The simple frequency data from the system should not, as is sometimes done, be used as a straightforward indicator of severity of abuse for any given substance (WOODS et al. 1987). Each visit involving drug abuse is termed an “episode”, and each drug being taken by the patient is termed a “mention”. As an example of the limitations of the data, in 3140 (17%) of the total 18,141 tranquilizer mentions, the kind of tranquilizer is “unknown”. The motive behind 62% of the mentions is given as suicide, which is not a form of drug abuse as the term is usually understood. Also, if a patient were taking diazepam for anxiety under a physician’s care and came to an emergency room after becoming paranoid on cocaine, both drugs would be coded as “non-medical” use. Using diazepam “mentions” as an illustrative body of data, in 1987, less than one fourth of the patients were on diazepam alone. Some 38% said the diazepam was legally prescribed. About 5% said they bought it on the street, and 53% of those mentioned listed the source as “unknown”. Half the diazepam episodes were suicide attempts, 15% were for “psychic effect”, and 20% were for “drug dependence”; for some 12%, no reason is known. From the longitudinal trend viewpoint, diazepam “mentions” are declining slowly over time, while alprazolam “mentions” are rising, presumably in parallel with the licit sales of the two agents. Incomplete numerical data such as these are frustrating. With 146,778 patient visits and 241,790 “mentions” of individual drugs in DAWN reports for 1987, one would optimally want a wealth of further data to get a better clinical idea of what is really happening. Chart reviews or, better, interviews with patients who are coded “psychic effect” or “dependence” would help provide an improved picture. Even with that, it needs to be kept in mind that people who have to go to emergency rooms may well not be typical of people abusing benzodiazepines as a total group. First, there are clear limitations on what one can expect data collectors to do in an emergency circumstance. A second major data system is the Client Oriented Data Acquisition Process (CODAP), which until 1982 provided patient data on all drug treatment facilities receiving federal funds, either exclusively or in part (since then the annual data have been less

comprehensive) (National Institute on Drug Abuse. 1982). These data say nothing about the medically prescribed use of drugs and, as such, chiefly are useful in studying the comparative prevalence of major drugs of abuse in persons sufficiently disordered to require treatment. For purposes of comparison, the percent of admissions in 1981 for heroin and marijuana were 36% and 19.4% respectively, while “tranquilizers” (again, chiefly benzodiazepines) constituted only 2.6%. Frequency of use data are provided for the month prior to admission, and the numbers are 75.9% for heroin, 41.9%. for marijuana. and 12% for tranquilizers. The use of tranquilizers as secondary or tertiary drugs is 2.5% and 1.7%‘. respectively. Also worth noting is that a higher percentage of primary tranquilizer abusers completed treatment without drug use than any other drug users. including alcohol users. On the basis of these general findings. we can say that for the group of people with serious drug abuse disorders, the benzodiazepines do show significant abuse liability, but it is fairly modest relative to several other more worrisome agents. DRUG ABLJSE TREATMENT STUDIES

There are also some limited data on benzodiazepine use in patients presenting for treatment of drug abuse problems or currently in methadone treatment. The federal government supported the Treatment Outcome Prospective Study (TOPS). a major treatment evaluation research effort, from 1979 to the early 1980s. TOPS collected a broad array of data on more than 11,000 patients undergoing various forms of drug abuse treatment (CRADDOCK et ~1.. 1985). Among a great many other things, this study reported on weekly or more use of minor tranquilizers. which ran from about 12-3 I %. depending on the year and cohort. Use of the benzodiazepines thus was not insubstantial in this group. Heroin. cocaine, marijuana, and alcohol use were predictably and significantly greater, and amphetamine use was roughly in the same range. Interestingly, this study collected data on the primary drug of abuse as perceived by the patients, and specifically separated out the category of Valium and Librium, which showed a very low incidence of being considered the primary drug of abuse. from 056 to 0.2%. depending on the group. (Overwhelmingly. heroin and other opiates were seen as the primary drugs.) Reports of proportions of urines positive for benzodiazcpines in patients attending methadone programs have varied very widely from clinic to clinic. Some experienced workers in the field have been concerned about the use of dia/,epam to “boost the high”. (KLEBER pt ~1.. 1978) and indeed some patients do use diazepam to potentiate the euphoriant effect of their methadone (BALL et al., 1983; STITZER ct ul., 19X1: GREI-ITHS c’t al.. 1987). A similar type of use has recently been described for alprazolam (WEDDIYGTON ct ul., 1987: FRASER, 1987). The severity and extensiveness of this problem is unclear. In a large ongoing study of methadone clinics in three major cities sponsored by the National Institute on Drug Abuse. BALL and colleagues (1987) find that, for each of the three cities. roughly 58% of the patients do not report any regular lifetime use of “sedatives” (chiefly benLodiazepinea, and excluding barbiturates). Since urines stay positive for benzodiazepines for more than a week after a moderate single dose of diazepam, one cannot determine from such frequency data whether use is episodic or regular. Some toxic screen methods in common use will not pick up alprazolam

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BENZ~DIAZEPINES ASDRUGS OFABUSE (FRASER, 1987). research.

The use of benzodiazepines

by opioid

addicts

clearly

needs

further

ABUSELIABILITYSTUDIES Animals can be induced to self-administer benzodiazepines (at least some animals under some conditions), but the drugs clearly are less reinforcing than barbiturates such as pentobarbital or stimulants such as cocaine or d-amphetamine (WOODS et al., 1987). It is striking that in studies involving human volunteers, diazepam and lorazepam neither produce subjective effects of euphoria nor are they chosen preferentially over placebo when the subjects are normal college students (JOHANSONef al., 1986; DE WIT er al., 1984) or even anxious individuals (DE WIT et al., 1986). Sedative abusers choose pentobarbital over diazepam, can distinguish between low and high dose pentobarbital but not low and high dose diazepam, and choose both drugs over placebo (GRIFFITHS et al., 1980). Damphetamine is preferred over placebo and is euphoriant in normal subjects (JOHANSONet al., 1986). In dry alcoholics who have recently undergone detoxification, single doses of diazepam (GRIFFITH et al., 1986; JAFFE et al., 1983; JASINSK~ et al., 1982) and chlordiazepoxide (JASINSKI et al., 1982a) and, to a lesser extent, halazepam (JAFFE et al., 1983; ORZACK et al., 1984) do show modest euphoriant effects in comparison to placebo. In our work with college students with histories of occasional recreational use of illicit sedative drugs, 20 mg diazepam almost always is significantly more euphoriant than placebo on appropriate scales of the Addiction Research Center Inventory (COLE et al., 1982; ORZACK et al., 1984; ORZACK et al., 1988; ORZACK et al., 1982). In these subjects, methaqualone is clearly more euphoriant than diazepam (COLE et al., 1982; IONESCU-POCCIA et al., 1988). Among the other benzodiazepines we have studied, prazepam (IONESCU-POGGIA et al., 1988), lorazepam, and alprazolam (ORZACK et al., 1988) at appropriate single dosages show subjective effect profiles roughly similar to diazepam at 20 mg, though alprazolam’s peak effect in a 2 mg dose was less marked and not significantly more euphoriant than placebo (ORZACK et al., 1988). Halazepam’s onset of action was much delayed relative to diazepam (ORZACK et al., 1984). Our other main criterion measures, which may have more relevance to the likelihood that a benzodiazepine will be abused if available through illicit channels, are the subject’s estimate, under double-blind conditions, of how much he or she would pay for the drug dose just experienced and his or her estimate of the likelihood of using that drug again. The likelihood of further use is recorded on a 16-centimeter scale with the mid-point being “maybe”, 16 “certainly”, and 0 “never”. On these measures, diazepam is regularly the highest of the benzodiazepines on both street value and likelihood of further use. The measures sometimes discriminate diazepam from other benzodiazepines, but regularly show methaqualone as more valuable and more likely to be used again than diazepam (COLE et al., 1982; ORZACK et al., 1988; IONESCU-POGGIAet al., 1988). One other study by GRIFFITHS et al. (1984) also used a “street value” measure comparing diazepam in single doses of 40 mg, 80 mg, and 160 mg with oxazepam at 480 mg. It must be noted that this study was done on a research ward, and the subjects, though drug free,

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had a recent history of barbiturate addiction. In an earlier study with similar subjects, 480 mg was the highest dose of oxazepam used in a protocol assessing dosages in a range of 10 mg to 160 mg diazepam and 30 mg to 480 mg oxazepam. These very high dosages were well tolerated by these subjects. At 480 mg, oxazepam was occasionally confused with placebo and received a mean street value of about $1.75, while diazepam at 160 mg was valued at $4.72, at 80 mg at $4.17 and at 40 mg at $2.75. Placebo was about 2Oc. Peak “liking” scores were significantly higher for all diazepam dosages (about 2.5 on a 3 point scale) versus about 1.5 for oxazepam and about zero for placebo. Diazepam was often guessed to be a barbiturate (67% of the time at the highest dose), while oxazepam was guessed to be a barbiturate only 21% of the time. Comments about both drugs showed favorable appreciation of diazepam’s rapid onset of action and its relaxing and sedative effects. Oxazepam caused mild relaxation, often with a dysphoric sluggishness or sleepiness. The authors attempted to construct relative rates of abuse of diazepam and oxazepam for the United States in 1980 and 1981 combined, correcting for the difference in sales figures (3600 million diazepam tablets versus 295 million oxazepam tablets). Given these corrections, diazepam was ten times as likely as oxazepam to be cited in DAWN “mentions” involving illicitly obtained drugs, and 21,000 times the amount of diazepam compared to oxazepam were seized by law enforcement authorities. Diazepam was stolen or lost eight times more frequently than oxazepam. These rough data, which contain the only law enforcement seizure data the authors have been able to find, fits with the experimental findings. Diazepam is, in fact, more abusable and illicitly used than oxazepam. DISCUSSION

The evidence, such as it is, suggests that benzodiazepines are very widely prescribed and not uncommonly taken for “non-medical” purposes, a vague and unsatisfactory category. Chronic benzodiazepine use seems to be mainly a mixed medical/psychiatric phenomenon occurring chiefly in older women, while “non-medical use” is commonest in younger men, who may occasionally use it “recreationally” or as one component of a more serious polydrug abuse pattern. Benzodiazepines seem to have little or virtually no reinforcing effects in normal experimental subjects. They do, however, have mild to moderate euphoriant effects in recreational drug users, detoxified chronic alcoholics, methadone patients, and, at very high dosages, in detoxified sedative addicts. A small proportion of patients coming to drug abuse treatment facilities list benzodiazepines as their primary drug problem. Methaqualone and shorter acting barbiturates such as pentobarbital probably are significantly more euphoriant than any benzodiazepine. Diazepam is more euphoriant and more extensively found by drug enforcement personnel than oxazepam. Other benzodiazepines are slightly less euphoriant than diazepam. To date, only diazepam and, recently, alprazolam have been reported to be abused to potentiate the effects of methadone by patients on methadone maintenance. It seems likely that drug abusers who prefer sedative drugs in large dosages will use a benzodiazepine when barbiturates are not available, and that polydrug abusers use benzodiazepines along with a variety of other drugs in ways not clearly described. Compared to cocaine, heroin,

BENZODIAZEPINES AS DRUGSOF ABUSE

marijuana, or even problem, given the authors of the most the benzodiazepines

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PCP and MDMA, benzodiazepine abuse seems to be a relatively minor vast amounts of benzodiazepines legally prescribed in this country. The recent, extensive review of the world literature on the abuse liability of conclude the following (WOODS et al., 1987):

Despite the wide availability and extensive medical use of benzodiazepines, there are very little misuse or recreational use of the drugs among adults or youths in the general population and little preference for them among populations of drug abusers; these findings parallel those of the experimental studies of self-administration.

This kind of relatively conservative impression of use has been expressed in other scholarly reviews (RICKELS et al., 1981; GREENBLATT et al., 1983). We would add, however, that this kind of impression is based on a less than ideal overall data base. For some, probably rather small but inadequately characterized groups of persons, benzodiazepine misuse is quite troublesome. Individuals who abuse benzodiazepines severely enough to become dependent and require detoxification appear not to be primarily street abusers trying to get high, but rather chronically dysphoric patients who originally began taking them as prescribed medication for their mood difficulties (JUERGENS et al., 1988). The serious street abuser seems to prefer more potent stuff. In this regard, there is suggestive evidence from GRIFFITHS et al. (1987) that repeated administration of 80 mg of diazepam every three days yields rapid waning of its euphorigenic effects. Better studies of a more clinical and anthropological sort, which reveal the exact ways benzodiazepines are used by serious drug abusers, are needed before we can accurately place benzodiazepine abuse into a useful and helpful clinical perspective. Optimally, we would want enough data to enable us to clearly demarcate the serious abuser and identify the psychiatric and medical patients who legitimately require significant doses of a benzodiazepine over protracted or indefinite periods of time but who may, on occasion, go on to various patterns of excessive use. Despite the pervasive use of these agents, and despite the extensive discussion they have drawn from the media, we still find relevant epidemiological data to be inadequate and unrevealing. High quality epidemiological studies into the misuse and abuse patterns of the benzodiazepines might well confirm our suspicion that these are second-order street drugs, used when more potent drugs are not available or as components of a polydrug disorder involving other, more clearly euphorigenic substances. More and better data on this subject are very much needed. REFERENCES ALBECK, J. (1988) Withdrawal and detoxification from benzodiazepine dependence: a potential role for clonazepam. .I. Clin. Psychiatry. 48, 43-48. BALL, J. C., SHAFFER, J. W., & NURCO, D. N. (1983) The day-to-day criminality of heroin addicts in Baltimore: a study in the continuity of offense rates. Drug. Alcohol. Depend. 12, 119.142. BALL, J. C., COREY, E., & MYERS, C. P. (1987) Methadone Research Project, National Institute on Drug Abuse. unpublished report. BALTER, M. B. (1987) The use of psychotherapeutic medications: an epidemiological perspective. In H. MeltTer, B. S. Bunney and J. J. Coyle (Eds.) Psychopharmacology: The Third Generarron. New York: Raven Press. COLE, J. O., ORZACK, M. H., BEAKE, B., BIRD, M., & BAR-TAL, Y. (1982) Assessment of the abuse liability of

buspirone in recreational sedative users. .I C/i/i. P.s~c~hicrt,~~.443. 6Y-75. CKADDO(‘K. S. G.. BRAY, R. M.. CGHI HHARD. R. L. (10X5)Drug u\e before and during drug abuse treatment: lY7Y1981, TOPS admission cohorts. Treatment Research Monograph Series, National Institute on Drug Abuse. DHHS no. (ADM) 85 13X7. Dr; WI.I, H., JOHANSON, C. E.. & UHL~~IWIII. E. H. (19X-I) The dependence potential of benlodiazeplnes. (‘~1.1: M& Rc.t. qxrr. 8. 4X-59. DI- WIT, H.. UHLENIIIItt1, E. H.. HI:III-KEK. D.. M~CK~CKEN. S. G.. & JOII.~USO~. C. E. (1986)Lxk of preference for diazepam in nnxious volunteers. An.11. Gcrr. P.v~c~hiot,-T. 33. SS3-541. FKASI:K, A. (lY87) Alpra~olam abuse and methadone maintenance. .I A.M.A. 258. 2061.2061. GRt:t:IUiiI.AT’r. D.. SHAIXZK, R.. 8r AH~RNEIIIY. D. (19x3) Current status of benzodia~epinea. Part II. N. EII,~/. ./. Mctl. 309. 3 I o-3 16. GKI~~I.II,s. R. R.. McLr.o~,. 0. R.. BI(;I.I.o~. G. E.. Llht~sc,r\. I. A,, Ro,\crlr.. J. D.. & Nowowr~ SK,. P. ( IOX4) Comparison of diofepam and oxarcpam: prefcrcnce. likin, ~1~md extent of ;lbusc. I P/lumruc~i~/. E.!/‘_7‘/w,:229, 501-.50x. GKlf:fIl~tS. R. R.. & S,\NYI:KI I). C. A. (IYX7) Ahuse of und dcpendencc on brnx)diaacpines and other anxiolytic/sedative drug\. In H. Melt/er (Ed.) P.~v~,hr,/,h~r,.,~rrr~.~~/~),~~: 771~ T/fin/ Thv. 215. 649.66 I. GKIFI.II’II. J. D.. JASINSKI. D. R., CAYEN, G. P., Xr MrKIVht?. G. R. (19X6) 1nvestig:ition of the ahuse Ilability of bu\pirone in alcohol-dependent patient\. An!. .I. Mccl. XO(Supp 38). 30-3.5. IoNI:sc.~~-Poc;c;I,\. M., BIKII. M., OKIA(K, M. II.. RI NI.S, F.. BI,,\KI:. B. J.. & COI.I, J. 0. ( IYXX) Methaqualone. //!r. (‘//I!. P.\JC /?/)/,/lu,_nl 3, Y7- I OY. J:\tbt.. J. H.. CtKr\rL.o. D. A.. Nu-.s. A.. Dlxoh. R. B.. Xc Mou~ot. L. (IY83) Abux potential of hala7epam and of dia/epam in patient\ recently treated for xute alcohol withdrawal. C‘lir~. Pkn/-n~c~~>/ Ther. 34. 633-630. JUINSU D. R., & JoIIhSoN. R. E. ( 10x2) Abuse potential of dla~epam (Valium). C/i!!. Plru/x?u~~~~/.Then 31. 226. JASINSKI. D. R., & Jo~iuso~. R. E. t I YX7) Ahuvz potrntinl of chlor~diaxpoxide. P/~~r~nrcrc,fj/o,~rsr.24. 133. JOII\NW~. C. E., & UIII I~NtlIfltl. E. H. (19x6) Drug preference and mood !n humans: dialcpam. P\VC h~,/‘/rcrf-nrcr[,,,/~~,~~71, x9-73. JOII~~,ION, L., O‘MAI I t\1. P. M., K: BU tth,hN, J. G. (IYX7) Nuri~~r~rrl 7;-0,1d., ,,I 111-q Us