Drug and Alcohol Elsevier Scientific

Dependence, 29 (1991) 107 - 143 Publishers Ireland Ltd.

Review

Chemical aversion Matthew

paper

treatment

0. HowardaVb, Ralph

of alcohol dependence

L. Elkins’.“,

(Accepted

Carl Rimmele’

August

9th,

and James

W. Smith’

1991)

Developments in the application of chemical aversion therapy to the treatment of alcohol dependence are discussed. Histc~ricxl factors leading to the early use of chemical aversion therapies are delineated and the theoretical underpinnings 01’ chemicxl aversion interventions are evaluated. Ethical and procedural considerations are a.ddressed and an assessment 111’the efficwc> of the therapy is attempted. Future research activities that would lead to refinement of chemical aversion therapy protocols are highlighted. The effectiveness of chemical aversion treatment of alcohol dependence is discussed vis-a-vis produc%iotr of con ditioned

alcohol-aversion

Key words:

chemical

and treatment

aversion;

outcome.

pharmacological

aversion;

emetic

aversirln:

Although 18 years have elapsed since Elkins’ (1974) and Davidson’s (1974) reviews of aversion conditioning for alcoholics were published, modern applications of chemical aversion treatment (CAT) continue to be controversial (American Medical Association, 1987; Elkins, 1991a; Hadley, 1985; Howard and Jenson, 1990a; McLellan and Childress, 1985; Miller and Hester, 1986b; Nathan, 1985; Office of Health Technology Assessment, 1987; Parloff et al., 1986; Wilson, 1987). One reason for the conflicting views voiced in the literature, with respect to the efficacy of CAT, is the paucity of controllCorrespondenw to: Matthew Howard, Addictions Treatment Center (116 ATC), Seattle Veterans Affairs Medical Center, 1660 South Columbian Way, Seattle, WA 98108 U.S.A.

Scientific

Publishers

treatment

ed clinical evaluations. In a highly critical account of CAT, Wilson (1987) comments that ‘The onus is squarely on the proponents of chemical aversion conditioning to show the specific and incremental efficacy of this technique, especially in light of the availability of alternative procedures that are superior on other dimensions of outcome’ (p. 513). Elkins (in press a) reaches a far different conclusion in his discussion of animal and human studies of CAT, finding that ‘Its proven effectiveness is also established to a degree that is at least equivalent to those of all other abstinence oriented treatments of alcoholism, medical or otherwise’ (P. 46). Other factors contribute to the current debate regarding the relative merits of CAT. Scant attention has been paid to either the historical tradition or theoretical foundations of phar-

Introduction

03768716/9X$03.50 01991 Elsevier Printed and Published in Ireland

alwh~~liam

Ireland

Ltd

108

macological aversion treatments. CAT protocols differ dramatically among studies, but have never been systematically examined. Concerns about ethical issues related to treatment of alcohol dependent clients with CAT have rarely been adequately addressed. Thus, this report identifies factors leading to the early application of CAT to the treatment of alcohol dependence. Ethical and procedural considerations are addressed, and evidence relevant to an assessment of the efficacy of CAT, vis-a-vis production of conditioned alcohol-aversion and treatment outcome, is reviewed. Historical

trends

in literature

and application

The idea of treating alcohol dependence by pairing the consumption of an alcoholic beverage with an aversive experience is ancient. Pliny the Elder, the Roman encyclopedist living in the first century A.D., lists a number of such techniques in his Historial Naturalis (Rackham, 1938). Among other things, the Romans placed spiders or eels in the bottom of wine cups to be found by the drinker while finishing his drink. More recently, Dr. Benjamin Rush, one of the fathers of American psychiatry, wrote that ‘The association of the idea of ardent spirits with a painful or disagreeable impression upon some part of the body, has sometimes cured the love of strong drink. I once tempted a negro man, who was habitually fond of ardent spirits, to drink some rum in which I had put a few grains of tartar emetic. The tartar sickened and puked him to such a degree, that he supposed himself to be poisoned. I was much gratified by observing he could not bear the sight, nor smell, of spirits for two years afterwards’ (Rush, 1815, p. 174). Rush further observed that ‘This appeal to the operation of the human mind, which obliges it to associate ideas, accidentally or otherwise combined, for the cure of vice is very ancient’ (p. 174). Descriptions of CAT are found in the writings of past literary masters. Anton Chekhov, the Russian dramatist, provides a gripping account of CAT in his story ‘A Cure for Drinking’ (Chekhov, 1960). The services of a hairdresser are enlisted to treat a famous comedian arriving

intoxicated to a small rural town. The hairdresser flashes a pint of vodka before the eyes of the comedian and elicits his attention, He then adds to the vodka a used piece of soap, saltpeter, ammonium chloride, alum, sodium sulfate, sulfur, resin and the ashes of a burned rag. Following a few self-administrations of adulterated vodka, the comedian becomes terribly ill. The next morning, the comedian, after rising, requests a drink of vodka. The hairdresser, responding to complaints that his treatment has failed to cure the comedian of his desire for alcohol, comments that ‘You might cure one of those weak fellows in five days, but this one has the constitution of a merchant. He’s tough’ (Chekov, 1960, p. 55). A number of other points are made by Chekhov (1960) with respect to the conditioning process. For example, the hairdresser notes that ‘in order to knock it [craving] out of him it is necessary to produce a revolution in all the organs and members of the body’ (p. 52). Other methodological issues appear to have been noted long before research arrived at similar conclusions. Anne Bronte emphasizes the need for including all plausible alcoholic beverages, in order to generalize effects of treatment, in her novel The Tenant of WiLdfeLL Hall. Bronte (1848) writes: I... I have succeeded in giving him an absolute disgust for all intoxicating liquors... [I] gave him quite as much as his father was accustomed to allow him but into every glass I surreptitiously introduced a small quantity of tartar-emetic -just enough to produce inevitable nausea and depression without positive sickness. Finding such disagreeable consequences invariably to result from this indulgence, he soon grew weary of it, but the more he shrank from the daily treat, the more I pressed it upon him, till his reluctance was strengthened to perfect abhorrence. When he was thoroughly disgusted with every kind of wine, I allowed him, at his own request, to try brandy and water, and then gin and water; for the little toper was familiar with them all, and I was determined that all should be equally hateful to him. This I have now effected; and since he declares that the taste, the smell, the sight of any one of them is sufficient to make him sick, I have given up teasing him about them, except now and then as objects of terror in cases of misbehaviour. and .._. when he was sick, I have obliged the poor child to swallow a little wine-and-water u.Gfhoul [italics added] the tartar emetic. because I am deter-

mined to enlist all the powers of association in my service: I wish this aversion to be so deeply grounded in his nature that nothing in after life may be able to overcome it.

(pp. SO- 72)

Many applications of CAT have failed to produce results as dramatic as those described by Rush and Bronte. Goodwin (1988) notes that Malcolm Lowry, the Canadian novelist, was treated twice with CAT in London Hospitals, going straight from hospital to pub on both occasions. The modern origins of CAT are traceable to the work of three Russian physiologists: Ivan M. Sechenov. Ivan P. Pavlov and. Vladimir M. Bechterev. Each of these scientists established the importance of conditioned responses in human behavior as elaborated by Kazdin (1978). Sechenov emphasized the role of the nervous system in learning and proposed that the empiric methods of physiology be applied to the study of psychological phenomena. Though there were some similarities in their work, Pavlov and Bechterev extended Sechenov’s research in different ways. Pavlov used conditioning procedures to examine aspects of nervous system functioning while Bechterev applied classical conditioning protocols to the treatment of psychiatric disorders. Babayan and Gonopolsky (1985) report that the idea of developing a conditioned ‘negative-defensive’ reflex to alcohol was repeatedly mentioned by Bechterev. The first clinical application of aversion therapy to the problem of alcohol dependence was reported by Kantorovich (1930) who treated 10 ‘confirmed alcoholics’ at Leningrad’s Psychiatric Hospital with ‘associated reflex therapy.’ Conditioned stimuli (sight and smell of alcohol) were presented with a strong electrodermal stimulus and ‘a stable defensive reflex was formed into patients’ (p. 493). Kantorovich maintained that most of the patients did not drink for months following treatment and that a comparative assessment of the effectiveness of this technique indicated its superiority to the other methods employed at the hospital. Western writers (e.g. Voegtlin and Lemere, 1942; Franks, 1963; Elkins, 1975) have credited Kantorovich with the first modern attempted use of

aversion therapy. However, based upon their reading of the abstracted report of his work, Rachman and Teasdale (1969) raise the possibility that aversion treatment may have been in use in other settings at the time of the Kantorovich report. In the earliest review of psychological, physiological and pharmacological methods of treating alcohol dependence, Voegtlin and Lemere (1942) describe research efforts employing pharmacological agents in aversion treatIn Russia, ment of alcohol dependence. Sluchevsky and Friken first used apomorphine to study conditioning in dogs (Galant, 1936). They then used apomorphine to treat 7 alcoholic patients with conditioned-reflex therapy; followup observations were not reported (Sluchevsky and Friken. 1933). Galant (cited in Lemere and Voegtlin, 1942) reported follow-up results of treating 22 patients with a modified version of the technique employed by Sluchevsky and Friken. Two patients remained abstinent for 1 year post-treatment; the remaining 20 reverted to drinking within 5 months of treatment completion. Voegtlin and Lemere (1942) cited other early reports (1934 - 1937) of apomorphine use during CAT alcoholism treatments by Dent (England), Ko (Belgium), and Fleming (United States). In France, hospitalized alcoholics were given a daily liter of ipecac-laced red wine for periods ranging from 3 to 8 weeks (Martimore and Maillefer, 1936, cited by Voegtlin and Lemere, 1942). At the end of treatment typical signs of revulsion were produced by pure wine. The authors noted that 40 of 45 patients displayed an aversion to wine 3 - 4 weeks afttbr the end of treatment. No other follow-up observations were reported. Alcoholism treatments involving nausea based CAT have been used in at least 75 international settings since 1933 (Elkins. in press a). The treatments typically have had some explicit linkage to conditioning concepts. However, this is not invariably true. A novel form of CAT is aclministered by Sangomas (witch doctors) in Swaziland, South Africa (Daniels, 1982).

110 a bottle. A mixture, which I cannot disclose, is then added to the bottle. The bottle is then subjected to pressure by burying it in the ground, for say a period of 6 weeks. I take this mixture and put it into the kind of brew my patient likes most. After taking the mixture he vomits profusely and feels sick. This treatment continues daily for about 3 weeks and then I give him a lighter treatment. I then encourage him to mix with bad drinkers. He does not drink but observes the foolish things they do. This, together with daily interviews with me plays the psychological part of the treatment. You see, I don’t want him to miss his old drinking friends. This continues for 3 months and then I can present him proudly to his family as a non-drinking man with a guarantee.’ (p. 5)

An important event in the advancement of behavior therapy in the United States was the establishment of Shade1 Sanitarium, in 1935, by Charles Shade1 (Kazdin, 1978). Between 1935 and 1950, over 5000 patients were treated at Shade1 Sanitarium with CAT. In the United States, a spate of reports about CAT, based on the treatment of alcoholics at Shade1 Sanitarium, were published (Lemere and Voegtlin, 1940; Lemere et al., 1942a, 1942b; Lemere, 1947; Voegtlin, 1940, 1947a, 1947b; Voegtlin, 1940; Voegtlin et al., 1941; O’Hollaren and Lemere, 1948; Voegtlin and Broz, 1949; Lemere and Voegtlin, 1950). These reports addressed diverse aspects of CAT treatment and presented early findings. Some specific topics, addressed in more detail below and elsewhere (Howard and Jenson, 1990a; 1990b; Elkins, in press a,b) included CAT protocols (Voegtlin et al., 1940) safety issues (Voegtlin et al., 1941) and the types of patients that are suitable for CAT treatments (Lemere et al., 1942a). Most of the reports, however, were interim assessments of treatment outcome (Voegtlin, 1940; Voegtlin et al., 1941; Lemere et al., 1942b; O’Hollaren and Lemere, 1948; Voegtlin and Broz, 1949; Lemere and Voegtlin, 1950). During the last 50 years, many other clinicians and a few researchers have attempted to assess the efficacy of CAT alcoholism treatment. These reports are discussed herein and/or in the above cited reviews or are documented in the annotated bibliography of the Addiction Research

Foundation of Toronto, Canada (Weise et al., 1975). A number of conditioning agents have been tried, but emetine, apomorphine or disulfiram were used within most settings. Thirty-nine treatment centers worldwide have used apomorphine as a CAT conditioning agent, and 15 have paired alcohol ingestion with adverse disulfiram reactions (Elkins, in press a). The Alcoholism Subcommittee of the World Health Organization in 1952 discouraged the use of disulfiram as a CAT conditioning agent; apomorphine and emetine were judged to be more appropriate for CAT alcoholism treatments (Glatt, 1962). A majority of all CAT candidates have received emetine, which has been the drug of choice within a number of large clinical alcoholism treatment programs in the United States. The old Shade1 Sanitarium, which has grown to three Schick Shade1 Hospitals, also gave rise to an independent chain of Raleigh Hills Hospitals. The Raleigh Hills chain expanded to a total of thirteen facilities (Elkins, in press a). Wiens and Menustik (1983) while discussing the promising results of CAT alcoholism treatment within a Raleigh Hills Hospital, noted that CAT had been featured within a few United States hospitals since 1935, and had become widely available in different states during the preceding decade. This availability has been greatly reduced since 1983. The Raleigh Hills Hospitals were sold and the new management terminated CAT alcoholism treatment. The only known United States present providers are three Schick Shade1 Hospitals. Rationale Modern chemical aversion alcoholism treatment began as a clinical adaptation of Pavlovian conditioning. In the United States, the Voegtlin and Lemere (1942) review concluded that traditional insight therapies had little to offer to alcoholism treatment. Voegtlin, a gastroenterologist who had studied Pavlovian conditioning, elected to effect a ‘. . . true conditioned reflex aversion to the sight, taste, and thought of alcoholic beverages’ (Lemere, 1987, p. 257). Toward this end his alcoholic patients viewed,

111

tasted and swallowed preferred smelled, alcoholic beverages before and during episodes of pharmacologically induced nausea and emesis. Voegtlin initially used apomorphine, but soon shifted to emetine, which he found to be a 1987). agent (Lemere, more satisfactory Voegtlin (1947a,b) reported that a majority of who received such treatment alcoholics developed conditioned aversive reactions. The follow-up abstinence rates of alcoholics treated via CAT within Schick Shade1 hospitals and their offshoot, the Raleigh Hills chain, are among the highest reported as documented within this review and in Elkins (in press a$). Early applications of CAT in different settings produced numerous examples of what appear to be genuine conditioned nausea/vomiting responses. Post-treatment nausea and vomiting following alcohol ingestion have been reported by Ajuriaguerra and Neveu (1938), Beaubrum (1967), Miller et al. (1960) and Quinn and Henbest (1967). Additionally, some treated alcoholics have reported or displayed nausea and/or vomiting to the smell (Aubertin, 1950; Rush, 1815/1972), taste (Dobroschke, 1953; Rush, 1956), and sight (Fischer, 1936; Williams, 1947; Desruelles and Fellion, 1951; Feldman, 1952; Mottin, 1973; Rush, 18150972) of alcoholic beverages. Shade1 (1944) reported that some recipients could no longer even read liquor advertisements without feeling nauseated. More recently, critically important psychophysiological and behavioral confirmation of successful conditioning during CAT was provided by Baker and Cannon and their associates (Baker and Cannon, 1979; Cannon and Baker, 1981; Cannon, Baker and Wehl, 1981; Baker et al., 1984; Cannon et al., 1986). Similar indices of conditioning had been reported during covert sensitization, a nausea based verbal aversion analogue of chemical aversion alcoholism treat.ment (Elkins et al., 1973; Elkins, 1975, 198Ob; Miller and Dougher, in press). These reports from the laboratories of Cannon, Elkins, and Miller contain suggestive evidence linking posttreatment abstinence to successful conditioning during the nausea-based treatments. For example, the CAT indices of conditioning included

decreased consumption, decreased affective ratings of the taste, and increased heart rate responses to the taste of target alcoholic beverages (Cannon and Baker, 1981; Cannon et al., 1986). Among alcoholics who relapsed following CAT, the indices of heart rate magnitude accounted for up to 25-30% of the variance in first drink latency (Cannon et al., 1981,1986; Sherman et al., 1988). Early clinical reports and more recent psychophysiological and behavioral observations lend credence to the therapeutic effectiveness of Voegtlin’s conditioning methodology. It is now abundantly clear, however, that the underlying conditioning process that subserves nauseabased CAT involves complexities that were foreign to Pavlovian conditioning as conceptualized during Voegltin’s era. These new complexities are apparent in (1) new findings within the field of Pavlovian conditioning and (2) in studies of consummatory aversion (CA) learning. An overview of these developments and their interfaces with CAT follows below. Rescorla (1988a,b), a leading proponent of Pavlovian conditioning, cogently argues that the reflex tradition of Pavlov and of many early behaviorists is now obsolete. This reflex orientation, which was derived from a long and respected tradition in physiology, falls to characterize adequately the circumstances that engender learning, the content of learning, and the manner in which learning is translated into performance. Rescorla (1988b) describes current trends as follows: Much modern thinking about conditioning instead derives largely from the associative tradition originating in philosophy. It sees conditioning as the learning that resuits from exposure to relations among events in the environment. . modern thinking about Pavlovian conditioning views associations as basic, but those associations are formed among representations of multiple events. Moreover, those representations themselves are often complex and include relations generated by other associations. Pavlovian conditioning does not consist simply of learning relations between a neutral event and a valuable event. Many different associations are formed, and the resulting content of learning allows a rich representation of the world. (p. 152 and p. 156)

Contemporary

Pavlovian

proponents

are stu-

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dying the types of problems that were once the purview of Gestalt theorists, and are current concerns of cognitive psychologists (Elkins, in press a). Chemical aversion alcoholism treatment was based on a conditioned reflex therapy that now is recognized as a simplistic view of Pavlovian conditioning. Additionally, some responses of humans that were originally considered to be simple reflexes are now known to be influenced by cognitive factors (Bridger and Mandel, 1965). Therefore, it is of considerable import to interpret advances within Pavlovian conditioning and cognitive psychology with respect to the modern application of CAT. Information relevant to CAT can be found in: (1) the emergence of CA learning, and especially to its major subcategory of taste aversion (TA) learning, as the central core of nausea-based aversion therapy alcoholism treatments; and (2) in the growing recognition that some learned responses such as nausea induced conditioned TAs may not require cognitive contributions during acquisition, and thereafter may be largely insulated from attenuation via cognitive mediation (Levy and 1987; and Martin, Sherman, Jorenby Baker,1988; Garcia, 1989; Wilson, in press). These developments have somewhat modified, but have also substantially strengthened the theoretical/empirical basis of Voegtlin’s treatment approach (Elkins, in press a). This analysis will explore implications of animal TA data for chemical aversion alcoholism treatments. Logne (1985) concludes that, when used with caution, both human reports and animal models may be useful in the development of a TA alcoholism treatment. Extrapolations from animals to humans must be made with caution; they should be viewed as working hypotheses until direct experimental support or refutation is forthcoming at the human level. However, it is of central importance to the present discussion to recognize that human TA learning has much in common with the TA learning of other species (Logue, 1985). Conditioned TAs are the most frequently studied conditioned CAs, but various combinations of sensory modalities are involved in the

CA learning of different species. For example, olfactory mediation has been observed in rats, and visual mediation is known to occur within some avian species (Riley and Clarke, 1977). Olfactorily, gustatorily, and visually conditioned CAs are common within humans as indicated above. For this reason the more general classification of CA is frequently used within this discussion. However, TA learning is a prominent part of the CA learning of both humans and rats (Logue, 1985). Conditioned CAs are phylogenetically old and exceptionally efficient learned adjustments having obvious implications for individual and species survival (Elkins, 1975). Conditioned CAs are readily acquired by many humans and rats when ingesta are appropriately paired with gastrointestinal distress involving nausea (Garcia, 1989). Such nausea can result from food poisoning, a variety of disease states, illness inducing drugs, motion sickness, or within some human alcoholics, from nausea-inducing verbal suggestions (Elkins, 1980a,b, in press a; Riley and Clarke, 1977). Conditioned TAs that endure for many years in humans, and for comparable extended durations in rats, are not uncommon following a single conditioning event (Elkins, 1973; De Silva and Rachman, 1987). Familiarity with the conditioned stimulus or unconditioned stimulus can impede the efficiency of conditioning, but strong TAs can be established through the use of repeated conditioning trials and discrimination training (Elkins, 1974). The efficiency of TA conditioning also is illustrated by the long temporal delays that can be tolerated between flavor exposure and subsequent illness onset. Such delays are common occurrences during TA learning that is based on food poisoning, X-ray exposure or chemotherapy in humans; successful conditioning in rats has been observed with CS-US intervals of up to 24 h (Estcorn and Stephens, 1973). Distal cues (e.g., color or odor) are normally weak CSs when conditioning is dependent on delayed nausea onset. However, if a taste cue is interpolated between the distal CS and subsequent nausea onset, then both the distal CS and the taste cue can become powerful

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deterrents to ingestion (Garcia et al., 1988). This phenomenon, taste potentiated learning, can be an important component of chemical aversion alcoholism treatment as will be illustrated below. Studies of conditioned CAs constitute an active area of investigation. This interest was fostered in part by landmark contributions of Professor John Garcia and his associates, and by an increasing recognition of the exceptional efficiency and the protective functional nature of TA learning. Garcia’s experimental and theoretical analyses identified and clarified the specialized efficiencies and limitations governing the learned associations developed between different classes of stimuli and responses. This work has a far reaching impact that extends to aversion therapy alcoholism treatments. Prior to findings from Garcia’s laboratory, little attention was paid to the specific influences that different types of stimuli and responses exert on the associative process. It was generally assumed that, given appropriate temporal and intensiany stimulus to which an ty parameters, organism naturally responded, and any response within the organism’s repertoire, could be readily linked through the process of conditioning. Garcia’s refutation of this assumption is discussed by Rescorla (198813): There is a kind of abstractness with which the descriptions of conditioning are often stated, an abstractness that is characteristic of a field seeking general principles. These descriptions suggest that conditioning occurs whenever one arranges a temporal relation among the events. The claim in essence is that the animal comes to conditioning with no preconceptions about the structure of the world. ready to accommodate itself to any world that it faces. Pavlovian conditioning has, of course. served as one of the pillars for radical empiricism. But in modern times it has become clear that this pillar itself is partly built on the existing structure in the organism. Not all stimuli are equally associable; instead, a stimulus may be easier to associate with some signals rather than others. The most well-known demonstration of this. of course. is Garcia and Koelling’s (1966) seminal work on the cue-to-consequence effect. They found that an internal distress was easier to associate with a gustatory rather than an auditory-visual stimulus, whereas a peripherally administered pain was more readily associated with the auditory-visual rather than the ~,rllStiltc~rp stimulus. (pp. 153- 154)

The therapeutic relevance of Garcia’s cue-toconsequence effect was recognized by Wilson and Davison (1969) who criticized the use of painful electrical stimulation of the skin and advocated instead the use of emetically induced gastrointestinal distress as a biologically approtherapy priate noxious basis for aversion alcoholism treatments. Garcia’s view of TA learning was influenced by Charles Darwin and Tolman (Garcia and Hankins, 1977; Garcia et al., 1988; Garcia, 1989). Darwin is considered to have set the stage for studies of CA learning. Darwin was concerned by an exception to his camouflage rule; caterpillars with brilliant color patterns displayed themselves openly on bare twigs and stems. Wallace hypothesized that these displays functioned to advertise the larval insects’ bitter taste and toxic properties to vertebrate predators (Darwin, 1871). Poulton (1887) supported this hypothesis by demonstrating that showy larval insects frequently contained a bitter tasting emetic toxin. Their vertebrate predators may consume one or more of these larval insects, experience illness, and thereafter reject similarly appearing specimens without any necessary physical contact. This is an example of a visually mediated aversion that, is probably acquired through taste potentiated learning (Garcia et al., 1988). Taste potentiated learning can play an important role in chemical aversion alcoholism treatments. Consider, for example, the report of Williams (1947). Williams laced bottles of spirits with an emetic agent that produced nausea onset about 15 min after ingestion. Following repeated pairings of the sight of a bottle and the taste of its contents with delayed onset nausea, treated alcoholics frequently vomited thereafter at the mere sight of the container. Garcia, in agreement with Tolman (1949). recognizes multiple kinds of learning. In addition to his field expectancies and cognitions, which can be subsumed under Pavlov’s CS-I!S and Thorndike’s R-US paradigms, Tolman described a distinct class of learning involving cathexis. Cathexis learning ‘. . is the acquisition by the organism of positive dispositions for

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certain types of food, drink, sex object, etc. or of negative dispositions against certain disturbance types of object’ (Tolman, 1949, p. 144). Garcia views TA conditioning as an example of negative cathexis acquisition and refers to Poulton’s (1887) analysis of predator avoidance of toxic caterpillars as Darwinian cathexis learning. Garcia stresses the special affinity with which the central nervous system components of vertebrates’ gut defense systems associate tastes with nausea. Garcia and his associates distinguish between learned avoidance responses that are based on the gut defense system and avoidance responses that are based on a skin defense system; they conclude that different neural associative mechanisms subserve two classes of learning based on these different protective mechanisms (Garcia and Ervin, 1968). Garcia (1989) emphasizes the occurrence of nausea-dependent hedonic shifts in taste that occur via the gut defense system during TA learning; post-ingestional nausea changes a palatable or an acceptable flavor in one having distasteful or repugnant gustatory qualities. The special role of nausea and the functional importance of hedonic shifts during CA conditioning have likewise been advanced by Rozin and Zellner (1985). Garcia (1989) discusses the brain’s emetic system and the critical role of nausea during TA acquisition via the gut defense system as follows: CFAs(conditioned

flavor aversions) have been discussed ad nauseum, which is entireiy appropriate for nauseous agents promote taste aversion: any physiological, emotional, or perceptual event or any physiochemical agent causing nausea will establish a taste aversion. The event or agent must affect the emetic system of the midbrain and brainstem. Allergies, bloating, and lower intestinal discomfort may cause a judicious subject to avoid specific foods but it will not cause a CFA (Pelchat, Grill, Kozin and Jacobs, 1983). CFA is an active dislike for the flavor of the food which can spread to the place where the food was eaten under special conditions; olfactory and visual cues associated with the feeding place will elicit signs of disgust in animals (Garcia and Rusiniak, 1980). Hearing or thinking about CFA elicits reports of nausea and facial expressions of loathing in humans. (p. 47 - 48)

Within the CA literature

a CS is usually con-

sidered to be a taste that has been rendered aversive through conditioning; nausea is the presumed 17s of such aversion acquisition. Garcia (1989) recently proposed the following reformulation. Feeding incorporates both Pavlovian conditioning and Darwinian cathexis learning. Taste reverts to its traditional role as a Pavlovian US. Environmental cues function as distal CSs that direct a subject toward food or away from danger during the coping phases of behavioral sequences. During feeding, taste is a pivotal US. Taste ends the cognitive CS-US coping sequence and initiates cathexis acquisition. During cathexis learning, the US undergoes an affective (hedonic) adjustment as a consequence of homeostatic feedback. During TA acquisition, feedback from a nauseous agent changes the hedonic value of the taste stimulus from one that is palatable or acceptable into one that is distasteful or repugnant. The process of TA acquisition is not dependent on any necessary cognitive or conscious process. Humans have a strong propensity to develop TAs to flavors that precede nausea even though they have a rational basis for believing that the flavor did not cause the illness (Logue, 1985). This is well illustrated by the seasickness induced ‘sauce bernaise’ phenomena (Garcia et al., 1985) and by TA acquisition during nausea based alcoholism treatments. Many alcoholics acquire aversions to alcoholic beverages despite being fully aware that the gastrointestinal distress that they experienced during CAT resulted from an emetic drug and not from alcohol ingestion (e.g., Cannon and Baker, 1981). Wilson’s (in press) revised analysis of controlled (cognitive) versus automatic processing during CTA is germane. He now recognizes the applicability to CAT of Pavlovian processing without attention or awareness. He cites recent empirical support in the human laboratory for Levy and Martin’s (1987) distinction between signal learning, which requires some degree of contingency awareness, and evaluative conditioning which requires no such awareness (Baeyers et al., 1988). Wilson characterizes TA learning as the prototypical chemical aversion conditioning procedure and depicts TA acyuisi-

tion as Darwinian cathexis learning which operates independently of cognition and awareness. Wilson (in press) concludes that there is now good reason to believe that there are different forms of classical conditioning having different associative processes. There are also relevant comparative animal data. Rats and humans apparently have in common an ability to taste saccharin shortly after it is introduced into the vascular system. Vascularly mediated TAs have been acquired by anesthetized rats when a tail vein injection of a dilute saccharin solution was followed by a typical illness inducing intervention (Roll and Smith, 1972). Additionally, Buresova and Bures (1973) have demonstrated that rats can acquire TAs under conditions of depressed electrocortical activity. In the words of Garcia (1989), ‘. . . cognitions, memories and awareness of the US-FB association are not necessary; simple disgust will protect the gut. . . . Nature is not constrained by semantic logic, it follows the functional logic of evolution. First evolve an affective system dependent on what is good or bad for survival: later evolve a cognitive system to determine what that is’ (p. 72). Belles (1985) advances the following functional analysis of Garcia’s position as explicated in Garcia et al. (1985). He refers to a system that defends the skin, the system that, in effect, defends the animal from external physical dangers; and he has a system that defends the gut, thr gastrointestinal tract. The first system has to be peculiarly sensitive to noises and lights and other external stimuli. (I emphasize the word ‘has’ to bring out the functional aspects of this system. It simply will not function functionally if it does not have this bias.) And the other system hns to be sensitive to the tastes and odors of foods. and it has to be sensitive to the consequences of ingestion. There is another differentiation: the skindefense system is rich in responses. Indeed, the whole point of such a system is to be able to produce adaptive motor behavior when the animal is confronted by an external threat. The gut defense system, on the other hand, is impoverished in terms of its response repertoire, but it can make a great variety of changes, and some very delicate changes, in the incentive value of taste and odor stimuli. Thus Garcia describes two separate systems designed to solve two separate kinds of problems, which it presumably does through quite different kinds 01

mechanisms It is perfectly clear to me that the coinditioned taste aversion phenomenon, the Garcia effect, transcends pure associations. We have to forget what we have learned to believe about interstimulus intervals and the equipotentiality or intersubstitutahility of stimuli. Certain kinds of motivational systems will select certain classes of stimuli that are relevant to the soluti(ln of its problems, The interstimulus interval also his to he relevant. The animal has to be able to associate events with time intervals like those that appear in nature. If’ we analyze motivational systems that have evolved to solve a certain class of problems, then the parameters that system works with have to be those that prevailed while the system was evolving. And if the parameters of this system violate the assumptions derived from o(hcLr systems, that is just too bad; different systems havca II) serve different functions. That is thr way the l’un~ tionalist thinks of it. (pp. I -2)

Bolles’s (1985) analysis of functional specialization is consistent with Seligman’s (1970) concept of associative preparedness. Seligman does not address specific biological substrates, but his position is consistent with the neuroanatomical diversity hypothesis presented by Garcia and Ervin (1968) and developed in Garcia’s subsequent reports. Seligman argued that evolutionary pressures have programmed the central nervous system to form readily, and specifically, associations between naturally related classes of stimuli (e.g., between taste and nausea). These ‘highly prepared’ associations are acquired more easily than are ‘unprepared’ associations (e.g., between external environmental CSs and painful electrical stimulation of the skin). At the other extreme of Seligman’s preparedness continuum, ‘contraprepared associations’ (e.g., between tastes and painful electrical stimulation of the skin) are considerably more difficult or impossible to establish, depending on the species and learning parameters under consideration. It is obviously possible for humans to develop cognitively mediated associations between tastes and shocks. However, such cognitively mediated aversions do not involve the gut defense system and do not endow a taste with negative hedonic qualities. For example, using rats as subjects, Garcia, Kovner and Green (1970) established a distinctive palatable flavor as a cue for shockmotivated shuttlebox avoidance. The flavor-

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shock pairings that were required to condition shuttlebox avoidance failed to decrease home cage preference for the cue flavor. However, pairing the flavor with illness produced a characteristic preference decrement. If the biological substrates and processes of the gut and the skin defense systems are ever fully explained, we will probably have a clearer understanding of why nausea, as opposed to painful peripheral shock, is the noxious basis of choice for aversion treatments of alcohol dependence. Individual differences in conditionability merit consideration. A minority of rats and alcoholics do not develop conditioned CAs despite exposure to appropriate conditioning methodologies. These conditioning failures include alcoholics treated with CAT who repeatedly displayed appropriate emetic responses (Voegtlin, 1947b) as well as alcoholics treated with covert sensitization who had numerous episodes of verbally induced nausea as confirmed by psychophysiological and behavioral measurements (Elkins, 1980b; Elkins et al., 1973). Vogel (1960) related Voegtlin’s CAT conditioning failures to individual differences in autonomic conditioning. Elkins (1973) suggested that individual differences in TA conditionability may be influenced by genetic factors. He advanced the working hypothesis that ‘. . . both rats and humans have evolved flavortoxicosis associative mechanism displaying intraspecific variability in the efficiency of aversion acquisition’ (p. 351). The animal component of the foregoing genetic hypothesis has been confirmed by the highly successful selective breeding of TA prone (TAP) and TA resistant (TAR) rats. The TAP and TAR lines have remained unsegregated with respect to shock motivated avoidance of a shuttlebox compartment, thereby supporting Garcia’s neuroanatomical diversity concept (Elkins, 1986). Additionally, TAP and TAR conditionability has been maintained with flavors and modes of aversion induction that differ from those which were used during selective breeding (Elkins et al., 1989; Elkins et al., 1990). The selectively bred lines, now in the 22nd genera-

tion of development, are producing TAP and TAR phenotypes for use in studies of biological bases of individual differences in TA conditionability. Current and planned research is directed toward neurotransmitter/neuromodulator hypotheses of differential TA conditionability (e.g., Aronstam et al., 1990). It is expected that the findings will eventually be reflected in biologically based screens that help to identify alcoholics who are appropriate CAT candidates. An additional long term possibility is the development of pharmacological (and/or perhaps dietary) interventions to increase the conditionability of TAR alcoholics (Elkins, in press a). It is important to recognize that both conditioned gastric reactions (i.e. nausea, vomiting) and negative hedonic shifts (acquired taste dislikes) are likely contributors to nausea induced CAs. Conditioned gastric reactions usually have been featured in reports of nausea based alcoholism treatments, while negative hedonic shifts in taste typically have been addressed in reports of TA studies of animal subjects. However, this dichotomy is by no means universal. Cannon et al. (1986) subjected their CAT alcoholic subjects to actual taste tests and palatability ratings. Garcia (1989), who is best known for his pioneering TA studies of animal subjects, observed that some humans who simply think about their conditioned food aversions report elicited nausea reactions and display facial expressions of loathing. Kiefer (1985). discussing both negative hedonic shifts and gastric reactions, proposed that a conditioned gastric response, mediated by vagal efferent fibers, may foster the maintenance of a conditioned TA. Simultaneous studies of conditioned gastric reactions and negative hedonic shifts within alcoholic CAT recipients are clearly indicated. The results may help to produce useful empirical bases for future studies and clinical judgments concerning CAT treatment duration and possible individualization of booster treatment schedules. It must be recognized that CAT cannot produce conditioned aversive reactions that will effectively block an alcoholic’s intended absti-

nence termination. A more realistic benefit of CAT is its likely facilitation of abstinence maintenance on the part of an alcoholic who is striving to achieve this goal. Toward this end the decreased desire for alcohol that has been reported by CAT recipients (Smith, 1982; Kerr and Sumi, 1985) may be an important rationale for CAT administration. A respite from cravings for alcohol may allow some CAT participants to pursue other activities and to develop lifestyle changes that can reduce the likelihood andlor severity of future relapses (Marlatt and Gordon, 1985). A conditioning based discussion of why decreased desire for alcohol should be expected from CAT appears in Elkins (in press a,b). Future experimental evaluations should include pre-treatment, within-treatment and posttreatment comparisons of desire for alcohol by recipients of CAT and other alcoholism treatments. Modern CAT evolved from the reflex tradition of Pavlovian conditioning. However, reflexology is no longer a complete foundation for the contemporary purview of Pavlovian conditioning or for CAT as explicated above. Rachman and Teasdale (1969) reasonably conclude that a rigid classification of CAT within either a classical or an instrumental conditioning paradigm is neither possible or desirable. They contend that CAT lacks the escape and avoidance contingencies of instrumental learning. However, this is an artifact of pharmacological nausea induction that does not apply to covert sensitization. Avoidance and escape contingencies can be prominent features of covert sensitization because verbal induction of nausea gives added flexibility within treatment sessions (Elkins, 1980a). Avoidance and escape concepts can be applied to the effects of CAT. See, for example, the two factor explanation of how escape from and avoidance of conditioned nausea may reduce alcohol related ideation (Elkins, in press a). The most fundamental current distinction that can be drawn between classical and instrumental conditioning is restricted to the procedural differences defining reinforcement within the two paradigms. Beyond this operational distinction, a two factor theoretical viewpoint has

widespread acceptance (Rachman and Solomon. 1967). However, even the distinction between a Pavlovian CS and a discriminative stimulus (Sd). which defines the availability of reinforcement for an operant response, is blurred beyond the operational level. Consider, for example, a light in an operant chamber which, when illuminated. is an Sd that defines the availability of food reinforcement for bar press responding. Well trained and food deprived rats usually will emit a bar pressing response shortly after light onset. Since the Sd presentation closely precedes food ingestion, after sufficient pairings with eating the light onset should also acquire CS properties with respect to salivation. Additionally, Rachman and Solomon (1969) present many examples which demonstrate that CSs can exert considerable degrees of control over instrumental responses. Recent studies of reinforcer devaluation are relevant to the interrelationships between the Pavlovian and instrumental paradigm and to a conditioning rationale for nausea based aversion therapies for alcoholism. It is now firmly established that performance of an instrumental response is strongly influenced by the current value of the reinforcer that was used to train that response. For example, Colwill and Rescorla (1985) trained rats to perform two instrumental responses, one of which was reinforced by pellets and the other by sucrose. One of the reinforcers then was paired with a toxin to reduce its value via TA conditioning. The rats later were given a choice between the two instrumental responses in the absence of any reinforcers; they displayed a strong preference for the response whose reinforcer had not been devalued. This line of research has been extended to discriminative stimulus control of instrumental behavior. Colwill and Rescorla (1990) found that reinforcer devaluation reduced Sd control of an instrumental behavior that originally had been based on that reinforcer. The implication for abstinent alcoholics’ avoidance of relapse is straightforward. An alcoholic who is depending solely on cognitive strategies to avoid alcohol consumption and instrumental habits that had previously led to

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drinking (e.g., approaching and entering bars) would appear to be at a higher risk for relapse than would an alcoholic who had supplemented the cognitive strategies with a successful devaluation of the alcohol stimulus via CAT or covert sensitization. This discussion has advanced a conditioning rationale for CAT alcoholism treatment. Modern CAT was originally based on the reflex tradition of Pavlovian conditioning. That early Pavlovian perspective is now recognized to be an inadequate explanation of CAT alcoholism treatment. Nevertheless, contemporary conditioning constructs continue to provide a cogent rationale for CAT alcoholism treatment. However, conditioning notwithstanding, it is important to recognize that other beneficial processes may be operative during CAT. The treatment is typically and appropriately combined with other therapeutic procedures. Such treatments may have as yet unknown synergistic interactions with CAT effects. This possibility is consistent with Beaubrum’s (1967) promising outcome with West Indies alcoholics who experienced combined CAT and AA treatments. Additionally, E.C. Miller et al. (1960) reported that group CAT alcoholism treatment appeared to enhance group cohesion and the participants’ selfesteem. They suggested that group CAT could facilitate receptivity to additional psychotherapeutic interventions. Williams (1950) noted with surprise encouraging therapeutic outcomes among apparent CAT conditioning failures; he suggested that the dramatic nature of CAT may increase receptivity to psychotherapy. These and other non-conditioning effects that may contribute to a CAT alcoholism treatment rationale merit experimental evaluation. However, it must be recognized that the only presently available experimental data that are relevant to a CAT alcoholism treatment rationale are results of studies of conditioning processes. Procedures A. Choice of unconditioned stimulus A number of pharmacological agents have been used to produce noxious states serving as unconditioned stimuli in CAT of alcohol depen-

dence. These agents include emetine hydrochloride (Voegtlin, 1940); apomorphine (Feldman, 1983); Syrup of Ipecac (Baker and Cannon, 1978, 1979; Cannon and Baker, 1981); lithium carbonate (Boland et al., 1978), disulfiram (Weise et al., 1975); metronidazole (Sansoy, 1970); ethanol (Ganesan, 1985); succinylcholine (Clancy et al., 1966; Madill et al., 1966); lycopodium (Babayan and Gonopolsky, 1985); sulfadiazine (Babayan and Gonopolsky, 1985); and antimony potassium tartrate (Lemere and Voegtlin, 1950). The Food and Drug Administration has not specifically approved these agents for use in CAT. Physicians may, however, prescribe agents for use in CAT that have not been approved for this purpose by the Food and Drug Administration*. Emetine hydrochloride is the agent most widely used in CAT. Thus, this review will focus on studies employing emetine as the unconditioned stimulus in CAT. Evidence pertaining to the molecular effects, pharmokinetics, and safety of emetine and other agents is available from Frawley and Smith (1989), Howard (1990), Howard and Jenson (1990a, 1990b), Loomis et al., (1986) and Manno and Manno (1977). Wilson (1987) argues that the use of emetine *In the foreward to the recent edition of the Physician’s Desk Reference, Barnhart (1990) comments that: Under the federal Food, Drug and Cosmetic (FD&C) Act, a drug approved for marketing may be labeled, promoted, and advertised by the manufacturer only for those uses for which the drug’s safety and effectiveness have been established. The Code of Federal Regulations 201.100(d) (1) pertaining to labeling for prescription products require that for PDR contents, ‘indications, effects, dosages, routes, methods, and frequency and duration of administration and any relevant warnings, hazards, contraindications, side effects and precautions’ must be the ‘same in language and emphasis’ (original italics) as the approved labeling for the product. FDA regards the words ‘same in language and emphasis’ (original italics) as requiring VERBATIM use of the approved labeling providing such information. The FDA has also announced that the FD&C Act ‘does not, however, limit the manner in which a physician may use an approved drug. Once a product has been approved for marketing, a physician may prescribe it for uses or in treatment regimes or patient populations

thut are not included in approved

labeling’

(italics added) (Foreward to the PDR, page unnumbered) Thus the FDA states that ‘accepted medical practice’ often includes drug use that is not reflected in approved drug labeling.

I l!)

in CAT is unethical because the FDA has not specifically approved emetine for use in the production of emesis in CAT and because the risks of emetic therapy outweigh the likely benefits. In this regard, it is relevant to note that the FDA has ruled twice in the past decade that no action to warn against the use of emetine in CAT is considered to be necessary (AMA, 1987; OHTA, 1987). Thus, accepted medical practice and recent rulings of the FDA appear to support the proljriety of emetic-based CAT. It is incumbent on the physician prescribing emetine for use in (‘AT. however, that a determination be made that the likely benefits of CAT to the patient outweigh the potential costs. This determination requires a thorough medical e:;amination of the patient and an awareness of the medical consequences and therapeutic effectiveness of CAT. These issues are discussed below. Several fatalities have been associated with administration of emetine hydrochloride in CAT of alcohol dependence. O’Hollaren and Lemerr (1948) report three deaths that might have been related to treatment: t\?o from coronary occlusion anal one from congestive heart failure. The study included a total of 2323 patients who had been trc%led between 1935 and 1945. Patients receive{! ;I total of 315 mg of emetine intramuscuktrly and 540 mg of emetine orally over a IO-day treatment interval. Histologic and electrocarclio~-r~~E)hic evidencae was not obtained and the role of emetine in these deaths is uncertain. Kattuinkcl (1949) reports the death of a 33-year-ok1 man receiving a total dose in excess of 750 mg of emetinr over I1 days. The patient evidenced no indication of cardiac abnormality prior to C.\T and death was attributed to toxic myocarciitis. An electrocardiogram was not administered immediateI>, prior to, or during. an electrocardiogram treatment. However, taken 1 week following treatment was ‘consistent wir h extensive myocardial damage.’ Kattwinkel ( 1949) noted that ‘In spite of a pounding heart. treatment with rmetine was continued, the symptoms being ascribed to the patient’s nervousness and emotional state’ (p. 995). It is tmport.ant to note that contemporary CAT protocols employ orally, rather than intra-

muscularly, administered emetine (Frawley, 1988). Intramuscularly administered emetine is far more likely to produce systemic toxicity than is orally administered emetine. In addition, the patient described by Kattwinkel(l949) received what. by today’s standards, would be considered an excessive cumulative dose of emetine. Taken together, these reports indicate the need for comprehensive medical and electrocardiographic assessment prior to, during, and following CAT. CAT is contraindicated for patients with esophageal varices, and cardiomyopathy (Kattwinkel, 1949; Howard and Jenson, 1990a). While several reports indicate that CAT produces evidence of generalized myopathy (Thimann, 194913; Sugie et al., 1984), Brem and Konwaler (1955) conclude that deaths due to emetine are exceedingly rare. This finding holds true for the years since Brem and Kowaler’s review (Howard and Jenson, 1990a;b). Lithium carbonate has also been used in CAT of alcohol dependence (Boland et al., 1978). Revusky and Gorry (1973) found that lithium produced more pronounced taste aversions than either emetine or apomorphine in samples of rats and squirrel monkeys. Pohl et al. (1980) report findings from animal studies that support the use of lithium over emetine. ipecac, disulfiram. and titrated calcium carbimide in taste-aversion treatment of alcohol dependence. Boland et al. (1978) report the only clinical investigation of lithium-based CAT. Eight of 25 (32’Yo) patients receiving lithium did not consistently become nauseous during treatment. At present, emetine appears to produce nausea and emesis more reliably than lithium in humans, although investigations of the potential utility of lithium in CAT of alcohol dependence are warranted. With the exception of emetine and lithium, the agents discussed above, and previously used in CAT, have little empirical support on which to recommend their use (How ard and ,Jenson, 1990a.b). Phtr rmncological adjuncts to CAT. Pilocarpine and ephedrine do not induce nausea and/or vomiting in therapeutic doses, but are often administered in emetine conjunction with

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(Voegtlin et al., 1940; Cannon et al., 1986). Pilocarpine is administered to close the pyloric sphincter thereby retarding absorption of alcohol. It also produces diaphoresis and sialorrhea (salivation) which early clinicians (e.g. Voegtlin, 1940) believed contributed to the establishment of conditioned alcohol-aversion. Ephedrine is given to combat the drop in blood pressure usually produced by nausea. Non-pharmacologic means of inducing nausea as an unconditioned stimulus. Although not the

focus of this review, it is important to note that a number of attempts have been made to associate visual, olfactory, and gustatory alcohol cues with nausea induced by nonpharmacologic means. Off-vertical rotation. Mellor and White (1978) used off-vertical rotation to induce motion sickness in alcohol dependent clients. Patients were seated in a chair that rotated about a 20” off-vertical axis at a rate of 17.5 rotationsimin. Treatments were administered on six consecutive mornings following an overnight fast. Subjects were ‘presented’ with a drink, then strapped in a chair, blindfolded and rotated. Four of 10 clients developed ‘aversive reactions’ to alcohol when they consumed alcohol at periods ranging from 5 to 10 weeks posttreatment, while 2 patients remained abstinent at 6 months follow-up. The Mellor and White (1978) conditioning procedure involved administration of two conditioning trials daily, requiring approximately 7- 20 min each, for 6 consecutive days. The procedure was efficient and safe; however, controlled trials are needed if the efficacy of this treatment is to be adequately assessed. Arwas et al. (1989) employed rotation-induced motion sickness as a US in their study of conditioned taste aversion in humans. Rotated groups drank significantly less than non-rotated groups following treatment. However, 9 of 20 rotated subjects failed to report any ill-effects from rotation. The authors reported that preconditioning exposure to the CS beverage impeded subsequent conditioning of a taste-aversion to the conditioned stimulus. Animal studies employing rotation in taste-

aversion experimental paradigms suggest that there is some promise in this method (Haroutunian and Riccio, 1973). Pseudo-coriolis effect. Lamon et al. (1977) capitalized on the Pseudo-Coriolis Effect (PCE) to produce nausea in their comparative assessment of faradic and nausea-based aversion therapies. The PCE is a visual illusion produced by having the patient tilt his head at a 45” angle to the left and to the right, while focusing on a moving visual field comprised of vertical lines. The PCE produces a feeling of profound disequilibrium and nausea. Once subjects in the PCE condition reported that they felt as if they were spinning, they were instructed to sip their preferred alcoholic beverage at the sound of each buzzer tone. Fifteen seconds after the patient reported that he was spinning, the buzzer sounded every 10 s until the end of the trial (duration unspecified). Lamon et al. (1977) reported that the PCE procedure produced a reduction in consumption of target beverages (fruit-flavored sodas) and found that conditioned aversions produced by the PCE procedure generalized to other fruit-flavored beverages. Covert sensitization. Covert sensitization can be viewed as a verbal aversion analogue of CAT. It involves repeated pairings of imagined drinking scenes with noxious verbal suggestions. These noxious suggestions typically emphasize nausea and vomiting and/or experiences involving fear and anxiety. Early investigations of covert sensitization yielded mixed results (Anant, 1967,1968a,b; Ashem and Donner, 1968; Cautela, 1966; Fleiger and Zingle, 1973; Hedberg and Campbell, 1974; Olson et al., 1981; Piorkowsky and Mann, 1975; Miller, 1976; Sanchez-Craig and Walker, 1982; Smith and Gregory, 1976; Telch et al., 1984; Tepfer and Levine, 1977; Wilson and Tracey, 1976). Elkins (1975) identified a number of procedural variations that possibly contribute to the disparate outcomes obtained to date. Recent studies have demonstrated that covert sensitization can produce conditioned aversions in a sizable proportion of treated alcoholics; additionally, successful conditioning was found to

be predictive of treatment outcome. For example, Elkins (1980b) reported the acquisition of conditioned nausea responses to imagined motivational and sensory antecedents and concomitants of alcohol ingestion in 46% of covert sensitization subjects. Among alcoholics who showed evidence of conditioning, 38% were continuously abstinent for intervals ranging from 6 to 72 months, compared to 12% of patients who failed to demonstrate conditioning. Elkins (1980b) emphasized the verbal induction of genuine visceral nausea as opposed to merely imagined aversive experiences. Additionally, both verbally induced nausea, and its subsequent conditioned counterpart, were defined via a combination of psychophysiological responses, self-reports and other behavioral observations. Miller and Dougher (in press), who systematically replicated (Sidman, 1960) and extended this methodology, demonstrated conditioned aversion to alcohol in 80% of their covert sensitization subjects. One-half of these clients were found to have ‘favorable’ treatment outcomes at 18 months follow-up. Comparative evaluations of CAT and covert sensitization are warranted, given the greater intrusiveness and intensity of CAT. Potential patient/treatment matching variables should be given special attention within such studies. Covert sensitization and CAT may prove to be maximally beneficial to different subsets of the alcoholic population. Additional discussion of CAT and covert sensitization similarities and differences appear in Elkins (in press a,b). B. Issues in conditioned administration

stimulus

(ethanol)

Studies examining the utility of CAT employ widely varying protocols. This variability is likely to introduce differential effectiveness, and may be a component in the sometimes contradictory outcome literature. The following are several important methodological issues in the application of CAT. 1. Timing of conditioned stimulus presentation. Until recently, most CAT protocols called

for administration

of the CS (alcohol) as close to

the peak of sickness as possible. For example, E.C. Miller et al. (1960) indicated that ‘only when the gagging begins, or when it seems likely that the individual is about to vomit, is it suggested that he drink the liquor’ (p. 428). Likewise, the subjects of Wallerstein (1957) and his associates did not enter the room in which alcohol was consumed until after the development of nausea. These procedures probably reflected: (1) the mistaken belief that vomiting is the US basis of CAT; and (2) given this misconception, the resultant efforts to achieve close temporal contiguity between the ethanol CS and vomiting, the presumed US. Nausea, not vomiting, is now recognized as the critical US of CAT conditioning. From this perspective the above described procedures are clearcut examples of backward conditioning. Franks (1963,1966) attributes many aversion therapy failures to inappropriate conditioning methodologies, and especially to the use of ineffective backward conditioning. However, ineffectiveness is not the only contraindication to the use of backward conditioning during CAT. Elkins (1970, 1975) argued that withholding the CS until after the onset of nausea could pair alcohol ingestion with the nausea relief that frequently results from vomiting. Such inadvertent pairings of drinking with relief from nausea could actually enhance, instead of decrease, the palatability of the alcoholic tlavor. Animal analogue support for this potentially disastrous CAT backward conditioning result was provided by Green and Garcia (1971). Rats acquired an enhanced acceptance of a flavor that was consumed during recuperation from apomorphine induced illness. In direct opposition to this conditioned flavor enhancement, a strong TA was acquired when the flavor exposure preceded illness onset. In the words of Green and Garcia (1971), “If the flavor is presented before the illness, the animal acts as if the flavor is ‘poison’. If the same flavor is presented during recuperation from that illness, the animal acts as if it is ‘medicine”’ (p. 741). Many early CAT practitioners apparently acted upon the prevailing view that very close CS-US temporal contiguity was necessary for optimal conditioning. This resulted in misguided

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efforts to insure that the initial CS ingestion within each treatment session occurred just before the onset of vomiting, the incorrectly assumed US. It is now well established that robust CAs can be acquired even when extended temporal intervals separate the CS exposure and the subsequent onset of nausea (Estcorn and Stephens, 1973; Logue, 1985). Recent CAT protocols have called for alcohol consumption either concurrently with (e.g. Boland et al., 1978) or shortly (approx. 5 min) after drug administration (Cannon and Baker, 1981; Cannon et al., 1986). In the case of emetine, between 5 and 10 min typically elapse before vomiting ensues. Additional attention to nausea onset is indicated. The most prudent current recommendation is to ensure that alcohol ingestion begins prior to the onset of nausea as opposed to vomiting. Experimental manipulation of CS-US temporal factors would contribute to the refinement of CAT protocols. 2. Concurrent interference. Concurrent interference occurs when ingestion of a consumable prior to illness attenuates conditioned aversion to a target substance by competing with the target flavor. Revusky (1971, 1973) found that single trial consumption of several substances before the induction of illness served to reduce the degree of conditioned aversion to each substance. Boland et al. (1978) and Revusky (1973) argue that treatment sessions should, therefore, be administered in the morning, before breakfast, so that exposure to flavored foods and beverages is avoided. Revusky (1973) contends that prior ingestion of an alcoholic beverage may interfere with development of a conditioned aversion to a targeted alcoholic beverage. ‘If aversion is to be induced to a familiar, mild tasting beverage, such as beer, a strong tasting, novel beverage should not be consumed before the induction of the sickness. The aversion to the strong-tasting substance would almost certainly interfere with the aversion to beer. However, aversion can be successfully established to each substance if it is consumed before separate occurrences of the sickness’ (Revusky, 1973, p. 16). Findings from

a series of animal investigations conducted by Cannon et al. (1985) support Revusky’s contention. They found that taste-aversion conditioning to familiar flavors was weakest when the ‘interference’ flavor was relatively more intense, novel, strongly associated with lithiuminduced toxicosis, and contiguous to toxicosis. Administration of the emetic agent in a flavored oral solution (Williams, 1947) or adding an emetic to an alcoholic beverage (Stojiljkovic, 1969) is not advisable given the potentially attenuating effects of concurrent interference on taste-aversion conditioning described above. At Schick Shade1 Hospitals, approximately 85 mg of emetine is administered in a saline solution during each CAT session. Anecdotal reports suggest that patients develop conditioned aversions to salt water following CAT. Currently, Schick Shade1 Hospitals are evaluating a treatment protocol calling for administration of emetine in only slightly salty water. Cannon and Baker (1981) took steps to reduce concurrent interference by having patients hold 30 ml of their favorite alcoholic beverage in their mouths following oral administration of ipecac before spitting it out. This was done so that the taste of alcohol, rather than ipecac, would be associated with the onset of nausea. They did not, however, evaluate the effects of this procedure on tasteaversion acquisition, retention, and generalization. In summary, it is advisable to administer treatments in the morning, following a period of abstinence from food and beverages (other than water). Although administration of several alcoholic beverages concurrently may attenuate aversions to each, the desirability of enhancing generalization of the conditioned response to a of conditioned stimuli, and other range pragmatic considerations, may necessitate some form of compromise. 3. Generalization of the conditioned aversion to a range of conditioned stimuli. The degree to

which different CAT protocols produce conditioned aversions across a range of alcoholic stimuli is not yet established. Lamon et al. (1977) found a nausea-based aversion treatment

protocol to produce reductions in target and nontarget beverage consumption (i.e. evidence of conditioned response generalization). However, beverages were all of a fruit-flavored nature and their similarity may have facilitated generalization. Other investigators report much different findings. Quinn and Henbest (1967) examined 9 patients treated with apomorphine who developed stable and prolonged aversions to one type of alcohol but who showed no generalized aversion to alcohol following CAT. Patients had abstained from whiskey, the CS used in conditioning trials, for post-treatment periods ranging from 3 months to 17 years. Three of the nine patients were considered ‘improved’ by self-report or wife’s report, but were currently drinking either beer or ale to excess, while 6 patients were regarded as unimproved. Of these six patients, two were drinking gin to excess, one stout to excess, one beer to excess, one rum to excess, and one wine to excess. Burt (1974) reports, in a study of 34 patients who relapsed following CAT, that 62% of the patients consumed, as their first post-treatment drink, their most preferred drink prior to treatment and the drink used in CAT trials. Baker and Cannon (1979) utilized a singlesubject design with multiple baselines across alcoholic beverages (bourbon, sherry, beer) and demonstrated that the amount of each alcoholic beverage consumed on taste tests was negatively correlated with the number of CAT conditioning trials to each beverage. Likewise, negative ratings of alcoholic beverages showed consistent increments as a function of the number of times the flavor occurred in conditioning sessions. Skin conductance and heart-rate responses to bourbon, sherry, and beer, increased with the introduction of each respective beverage into CAT conditioning trials and with the number of times the flavors occurred in conditioning trials. CAT was found to be effective in producing psychophysiological, behavioral and attitudinal evidence of conditioned aversion to alcohol and strength of taste aversion was demonstrated to be a function of number of conditioning trials. This latter finding has also been reported in the

animal literature (Cannon et al., 1975). In general, there was little evidence of generalization of conditioned aversion across substances. Clinical investigations of CAT have used different methods of attempting to facilitate generalization of the conditioned aversion to a variety of alcoholic beverages. Boland et al. (1978) analyzed the patient’s past preferences for alcoholic flavors along a continuum of novelty-familiarity. Each drink was then paired with sickness, starting with the novel and ending with the most familiar. The authors concluded that this procedure capitalized on flavor novelty which is known to be an important factor in aversion strength (Revusky and Taukulis, 1975), and might serve to diminish the familiarity of the more frequently consumed beverages. A number of investigators administer a variety of alcoholic beverages during treatment, with particular emphasis on the patient’s preferred beverage, but there is no standard procedure for administration of multiple beverage types (Cannon et al., 1986; Neubuerger et al., 1980). Future research should examine various protocols with respect to the degree to which they facilitate generalization of the conditioned response to a range of alcoholic beverages. At present, predominant emphasis on the patients’ preferred alcoholic beverages during CAT appears justified (Burt, 1974). 4. Optimal Amount of CS (ALcohol) Consumption. CAT programs typically employ protocols

calling for the consumption of voluminous quantities of alcohol (Smith, 1982). Patients usually do not become intoxicated because they vomit repeatedly daring conditioning trials. Because vomiting is associated with medical complications such as Mallory-Weiss Syndrome and rupture of the esophagus, CAT without vomiting would be considerably safer. Cannon et al. (1986) report no differences, vis-a-vis production of conditioned aversion or treatment outcome, between patients who swallowed alcohol during CAT trials and those who were administered alcohol via a ‘smell, swish, and spit’ protocol. Data obtained with rats (Domjan and Wilson, 1972; Revusky et al., 1976) suggests that CAT pro-

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tocols produce stronger aversions when the target beverages are actually swallowed, as opposed to passed over the tongue, prior to illness. Domjan and Wilson (1972) found no incremental advantage in allowing rats to consume comparatively large amounts of alcohol. On the basis of Domjan and Wilson’s findings, Boland et al. (1978) had subjects swallow the equivalent of 30 ml of absolute alcohol during CAT trials. Based on the above, somewhat contradictory findings, a reasonable clinical approach would be to recommend that a small amount of alcohol be swallowed during CAT trials. The consumption of voluminous quantities of ethanol appears unnecessary and is potentially dangerous. 5. Intosication. Most clinicians emphasize that intoxication produced by alcohol consumption during CAT must be avoided at all costs. Subjects who are unable to vomit, despite severe nausea, have their stomachs emptied via gastric lavage. Voegtlin (1940) argued that absorption of ethanol to the point where an effect is noted by the patient would vitiate the entire treatment. Pavlov (1928) cautioned that sedative agents disrupted formation of conditioned reflexes and since the early 1930s clinicians have taken care to avoid this situation. Kant (1944; 1950) reports that the strength of the conditioned aversion produced in CAT is diminished if the patient becomes intoxicated. Currently, absorption of alcohol is rarely a problem; onset of nausea typically occurs 8- 16 min following administration of emetine, with emesis of alcoholic beverages occurring shortly thereafter. 6. Administering the conditioned stimuhs: temperature, carbonation, and percentage of ethanol in the solution. Investigations of CAT

differ with respect to the temperature, dilution, and degree of carbonation of the alcoholic beverages used as conditioned stimuli. Cannon and Baker (1981) diluted distilled spirits and served beer warm and wine and spirits at room temperature. Beer was served flat. The authors justified their procedures by noting that cold spirits are not regurgitated easily and that effer-

vescence with emesis. interferes Mixing alcoholic spirits with water provides a volume of fluid for emesis and helps prevent dehydration. In addition, it reduces the potency of the beverage. Smith (1982) describes the Schick Shade1 protocol and states that carbonated beverages are never mixed with the alcohol nor is ice ever added to the beverage, because both are associated with appropriate non-alcoholic beverages. In addition, he contends that both tend to diminish the sensations of odor and taste of the alcoholic beverage and are thus contraindicated during treatment. He suggests that warm water be mixed with the beverage serving as the eonditioned stimulus in order to bring out the odor and the flavor more strongly. On a theoretical level, one might expect that administration of beverages at the temperature and strength and in the mixtures commonly encountered in the client’s environment, could enhance generalization of treatment effects from the hospital to the client’s experiences outFuture research should side the hospital. evaluate the effects of factors related to conditioned stimulus (alcohol) presentation on condiacquisition tioned alcohol-aversion and retention. 7. Preconditioning

familiarity

with the condi-

tioned stimulus and the unconditioned stimulus. Elkins (1974; 1980a) used animal data to address the likely effects of preconditioning familiarity with the CS (alcohol) and US (nausea) on the efficacy of nausea-based alcoholism treatments. Elkins (1984) questioned the clinical relevance of available demonstrations that preconditioning CS or US familiarization can disrupt subsequent TA acquisition; it was noted that the reviewed studies typically used only one (or a few) TA conditioning preconditioning trial(s). These familiarity-effect demonstrations also lacked any explicit use of discrimination training, an important aspect of aversion therapy methodology (Elkins,in press a). Elkins (1984) studied preconditioning CS familiarity effects on rats while using procedures that more closely modeled CAT alcoholism treatment. He combined

multiple conditioning trials with discrimination training, thereby producing strong TAs to a highly familiar and bland fluid, laboratory tap water. This confirmed the transitory nature of disrupted TA acquisition as a consequence of preconditioning familiarity with the CS flavor. Elkins (1980a) likewise found that disrupted TA acquisition via a history of preconditioning US exposure is reversible given multiple conditioning trials and discrimination training. These results obviate the Amit and Sutherland (1975) concern that preconditioning familiarity effects TA based alcoholism may contraindicate treatment.s. The CS familiarity effects also can be attenuated by the process of forgetting. Rats failed to acquire conditioned TAs immediately following a flavor familiarization procedure, but acquired significant and equivalent TAs when conditioning was delayed for either 20 or 100 days after familiarization (Elkins and Hobbs, 1979). Thus, the efficiency and cost-effectiveness of CA approaches to the treatment of alcohol dependence might be enhanced by a period of abstinence from alcohol prior to treatment with CAT. Future research should evaluate variable periods of preconditioning abstinence from alcohol, so that the optimal interval for purposes of’ conditioning can be established. C. Additional m,ethodological issues pertaining to CAT protocols. 1. Number qf CS-USpairings. CAT protocols

differ with respect to the number of conditioning trials employed during the course of treatment. Miller et al. (1960) administered 10 sessions over 2 weeks, allowing weekend rest periods. Voegtlin (1940) reports use of five to seven treatments with l-day rest periods between each treatment. Thimann (1949a) reports daily treatment with CAT for 5 - 6 days. Carter (1943) found four to eight trials effective in developing conditioned aversion to alcohol. Boland et al. (1978) employed six conditioning trials spaced 2 days apart. Most contemporary applicat,ions of CAT employ five conditioning trials, each 48 h apart (Cannon et al., 1986; Smith, 1982; Wiens and Menustik, 1983).

A number of empirical issues are unresolved vis-a-vis determination of the optimal amount of conditioning. First, it is not clear when the client has received ‘enough’ conditioning within a given conditioning trial. That is, it is unclear when the session should be terminated. Clinical studies of CAT have never evaluated the differential effectiveness of variable criteria for termination of CAT trials. Many therapists terminate CAT trials once the client has consumed, and returned as vomitus, a predetermined number of alcoholic drinks. If the patient fails to vomit, emesis is induced by having the patient insert a finger into the throat, or if that is insufficient, gastric emptying is accomplished via a gastric tube (Smith, 1982). 2. Booster sessions. Elkins (1984) establishes the susceptibility of conditioned consummatoryaversions to the processes of extinction and forgetting (reduction in aversion strength during post-treatment periods when patients do not consume any alcohol). Rats receiving low doses of an emetic developed conditioned aversions that were forgotten within 20 days and were susceptible to extinction, while rats receiving a high dose of an emetic developed consummatory aversions that were highly resistant to aversion degradation. These findings suggest the need for induction of intense nausea during conditioning trials and imply that periodic conditioning trials (booster sessions) may be important to alcohol-aversion retention. Post-treatment aversion sessions, also known as ‘booster sessions,’ ‘reinforcements,’ or ‘recaps,’ are administered by clinicians in highly diverse manners. Boland et al. (1978) did not employ booster sessions. Cannon et al. (1986) used six booster sessions scheduled at progressively longer post-treatment intervals. Patients who failed to maintain continuous sobriety sinct discharge from treatment could not participate in booster sessions without completing some period of intensive treatment. Carter (1943) employed three booster sessions at 2, 4, and X months postdischarge. Thimann (1949a) used 6 - 7 booster sessions at intervals ranging from 4 to 12 weeks. For patients who so desired. four

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booster sessions were given at 3-month intervals during the second year post-treatment. Schick Shade1 Hospital routinely administers booster sessions at 1 month and 3 months following discharge from the hospital (Smith, 1982). A small percentage (5- 10%) of patients are administered additional booster sessions. Wiens and Menustik (1983) tailored the number and timing of post-treatment reinforcement trials to the needs of the patient. At present, it is not possible to recommend an optimal number of reinforcements or to specify the post-treatment period over which they should be administered, given the dearth of controlled studies evaluating the effects of different booster session treatment regimens on alcohol aversion retention and treatment outcome. Tailoring booster session treatment regimes to clients is not yet feasible due to lack of knowledge of factors predicting susceptibility to, and longevity of, conditioned alcoholaversions. 3. Nausea versus emesis. The respective roles of nausea and emesis in aversion acquisition needs to be determined. Several medical risks attend vomiting suggesting that aversion acquisition without emesis would be safer. Raymond (1964) found that strong conditioned aversions could be developed in subjects with nausea alone and without the need for actual vomiting. Cannon et al. (1986) randomly assigned subjects to one of two emetic aversion procedures. In one group, subjects smelled the alcoholic drink, swished it in their mouths, and spat it out without swallowing it. The procedure in the other group was similar except that subjects swallowed the alcoholic beverages, received a higher dose of emetine, and frequently vomited. Groups did not differ significantly in latency to onset of self-reported nausea (mean = 8.9 min), nor did they differ in incidence of 15 symptoms (e.g. sweating) reflective of nausea rated 20 - 30 min after conditioning trials. Treatments differed with respect to incidence of medical complications, with the group swallowing the alcoholic beverage more likely to experience medical complications. Cannon et al. (1986)

found no differences between groups on any aversion or treatment outcome measure. Since patients in the non-swallowing group rarely vomited, the Cannon et al. (1986) findings suggest that emesis is not necessary for the conditioning of alcohol aversions. Gamzu et al. (1985) also present evidence supporting the claim that emesis is not a necessary, but may well be a sufficient, condition for the induction of tasteaversion. 4. Potential new developments in administration of chemical aversion therapy. a. Group Administration. In the United

States, CAT has, almost without exception, been administered to patients individually. Miller et al. (1960) report that of their 20 patients undergoing CAT in groups all acquired conditioned alcohol aversions to all forms of alcohol presented to them. The anecdotal nature of this report, the poorly described follow-up procedures, and the small sample size of this study limit its usefulness. The E.C. Miller et al. (1960) report does suggest, however, an avenue for reduction of costs associated with CAT. CAT is commonly employed with groups of patients in the Soviet Union (Babayan and Gonopolsky, 1985). 6. Indwelling pump. Another potentially useful procedure could be implantation of an instrument analogous to the glucose insulin infusion device currently in use for treatment of diabetes, but delivering an emetic in response to a given blood ethanol level (Brown, 1983). Monitoring of blood ethanol levels could be either intermittent or continuous, and release of the emetic could be made contingent upon attainment of a predetermined blood alcohol level. Ethical

considerations

Application of aversive techniques to treatment of behavioral problems by members of the helping professions is controversial. Rachman and Teasdale (1969) comment that ‘We have mixed feelings about aversion therapy. On the

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one hand we are interested in it as a psychological process and welcome the introduction of effective treatment procedures. On the other hand, we recognize that it is an unpleasant form of therapy and one which is open to abuse’ (p. xi). The mixed feelings of the profession toward aversion therapy are indicated by the few published books on the topic. Rachman and Teasdale (1969) published the most recent guide to clinical issues in aversion therapy and, until the recent publication of Hadley’s (1985) theoretical account of aversion therapy, nothing had been written in book form on the topic for two decades (Clarke and Saunders, 1988). Franks cautions practitioners on the use of CAT in the introduction to Hadley’s (1985) book: Aversion therapy remains a sensitive issue on numerous accounts and it behooves the behavioral clinician contemplating its use to proceed with caution. First, it is essential to be thoroughly familiar with the intricacies. strengths and weaknesses of the theory, data and research upon which the practice of aversion therapy is predicated. Second, it is important to avoid aversion techniques deployed in isolation rather than as part of a planned program involving positive as well as negative strategies. Third, an aversion or punishment procedure (the twcb &rms are essentially synonymous) should be used only when the available evidence suggests on theoretical, research and pragmatic grounds that, for a particular purpose, it is the most acceptable alternative. Fourth, decisions with respect to usage should never he predicated upon the say-so of the therapist alone (p. viii).

Medical and behavioral science is increasingly confronted with the paradox that discomfort is often integral to the application of effective treatments. Contemporary health-professionals, for example, must square Hippocrates’s admonition to the young physician that he ‘. . . prescribe regimen for the good of . . . patients according to . . . ability and . . . judgment and never do harm to anyone’ with modern cancer chemotherapy,, a procedure that is both for the good of patients nnd highly toxic (Bulger, 1973, p. 3). Likewise, insulin is helpful to the diabetic patient, but can cause dangerous, and even fatal, hypoglycemia. Members of the helping professions are aware that therapeutic interventions often bring adverse consequences to patients, in addition to those that are ameliorative. They attempt to be sure, however, that the ‘cure’ is no

worse than the disease and that no other equally or more effective alternative, and less toxic, treatment is available. In addition, they make a reasoned assessment of the consequences that are likely to be experienced by the patient, should interventive measures fall to he initiated. Smith (1982), for example, cautions that although aversion treatment sometimes comes under attack as a treatment modality because it involves causing discomfort for the client, one must consider the alternative. Continued drinking or multiple relapses frequently lead to death and disability, and to dissolution of family and other social ties. Smith (1982) contends that selfdestructive behaviors, such as alcohol dependence, should be brought under control as quickly as possible. For this purpose, he argues, CAT is appropriate. The argument that the discomfort caused by aversion techniques renders them unethical is, as Wilson (1978) properly notes, a mluctio cld absurdurn. Wilson (1978,1987) identifies a number of legitimate ethical issues in CAT atiministration which are delineated below. Wilson (1978) notes, in agreement with the position taken by the American Psychological Association, that all patients receiving CAT should give their informed consent to the intervention, following a detailed description of the treatment procedures vis-a-vis their effectiveness and side effects. In studies of CAT of alcohol dependence with succinylcholine, clients were frequently not informed in detail as to what the treatment would entail. Clancy et al. (1966) simply told clients that if they accepted treatment they ‘would be given a drug and tested with an alcoholic beverage in order to cause a reaction’ (p. 477). Given the traumatic nature of this intervention, described hy one illvestigator (Holzinger et al., 1967) as ‘an agonizingly long period of helpless waiting in a growing panic of fear,’ failure to obtain informed consent is particularly inappropriate. In addition, alternative therapies should be discussed with the patient, particularly with respect to their efficacy and safety. It is the patient’s prerogative, of course, to revoke consent to any aspect of therapy at any point in time.

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Wilson (1987) contends that current application of CAT is unjustified because: (1) the treatment is highly intrusive. By this Wilson means that there is a high degree of ‘obvious external control’ (especially aversive control) and that there is a relatively high degree of stress or discomfort inherent in application of the intervention. He argues that the principle of the ‘least intrusive alternative treatment’ demands that CAT be employed only after less intrusive interventions have been tried and found to be ineffective; (2) CAT is unacceptable to the majority of professionals and clients in the alcohol dependence treatment field. This is viewed as the reason that the technique has not been more widely used. Wilson does not offer any empirical support for his contentions, but concludes that the grueling nature of the treatment, will render it unacceptable to many alcoholics; (3) alternative forms of treatment are available which are safer, cheaper, and at least equally effective. Use of CAT is unwarranted, except when alternative treatments have been tried and found to be ineffective; (4) CAT is not as cost-effective as equally effective alternative treatments which are currently available; and (5) CAT is less safe than non-invasive alternative treatments which are, putatively, equally effective. Wilson concludes that the onus is on proponents of CAT to demonstrate, in methodologically sophisticated randomized clinical trials, that CAT is associated with superior treatment outcomes, otherwise its use as a first line of treatment cannot be ethically justified. Current criticisms of CAT of alcohol dependence are addressed in detail by Elkins (in press a,b) and by Howard and Jenson (1990a,b). They conclude that the treatment as currently employed is not unduly intrusive. Informed consent is routinely obtained from clients and the discomfort experienced by patients is warranted given the demonstrable effectiveness and safety of the treatment (Loomis et al., 1986; Miller and Hester, 198613). As regards the acceptability of the treatment, what little data are available suggest that patients find the treatment acceptable (Boland et al., 1978) and withdraw prior to treatment completion at a comparatively low rate

(CATOR, 1985). The acceptability of CAT to different client populations is an empirical question deserving attention. Recent reviews of the alcohol dependence treatment outcome literature (e.g. Miller and Hester, 1986b) indicate that CAT is a promising therapeutic modality and that few studies have compared the effectiveness of CAT and other treatment modalities. With respect to safety, a recent toxicological analysis (Loomis et al., 1986) suggests that the use of emetine hydrochloride in the oral doses commonly employed in CAT is unlikely to be associated with any significant toxicity. In sum, the criticisms of CAT forwarded by Wilson (1987) suggesting that the use of CAT as a first line of treatment is ethically unjustified, are premature in some cases and erroneous in others. We concur with Wilson (1987) that controlled clinical trials are needed if the full merit of this approach is to be determined. Effectiveness Because emetine hydrochloride is the only agent currently in use in the United States for CAT, emphasis in this section will be on clinical reports employing this agent. Two issues are relevant to the question of the effectiveness of CAT: (1) To what extent does CAT produce objective evidence of conditioned aversion to alcohol? and (2) To what degree is conditioned aversion to alcohol predictive of treatment outcome? 1. Production

of conditioning

Although the CAT literature is among the most extensive in the alcohol dependence treatment field (Weise et al., 1975; Center of Alcohol Studies, 1978; Miller and Hester, 1986b), few studies have examined whether CAT actually produces conditioned aversion to alcohol. Baker and Cannon (1979) Cannon and Baker (1981), Cannon et al. (1986) report the strongest evidence to date supporting the capacity of CAT to produce conditioned aversion to alcohol. In two single-subject studies (Baker and Cannon, 1979) they used a multifaceted approach to the assessment of conditioned alcohol aversion and found decreased alcohol consumption during taste

tests, increased negative ratings of alcohol on an adjective checklist, and increased skin conductance and heart-rate responses to presentation of alcohol, following CAT. In another study, Cannon and Baker (1981) randomly assigned 20 alcohol dependent subjects to either CAT, shock aversion therapy, or to a control group. Compared with the control and shock groups, CAT subjects exhibited significantly larger increases in heart-rate responses to alcoholic beverages, reported more negative attitudes towards alcohol, and displayed more behavioral signs of aversion, during post-treatment taste tests. Similarly, Cannon et al. (1986) observed that conditioning with emetine hydrochloride and Syrup of Ipecac, using two different aversion treatment protocols, produced increases in heart rate and electromyographic responses to alcohol, increases in negative attitudinal ratings of alcohol, and decreased consumption of alcohol, on post-treatment taste tests. Further, Cannon et al. (1986) report that the magnitude of the conditioned alcohol-aversion was not significantly correlated with any of the demographic variables they examined. Elkins’ (19SOb) finding that verbal aversion treatment (covert sensitization) of alcohol dependence produces conditioned nausea to alcohol, reflected by changes in galvanic skin response and respiratory and digital pulse, is also relevant. Thus, there is evidence from recent investigations suggesting that CAT produces conditioned aversion to alcohol. Wilson (1987) acknowledges that the Cannon and Baker (1981) study ‘is important in demonstrating that chemical aversion therapy conditioning did establish conditioned aversion reactions to alcohol at post-treatment. This demonstration is, of course, fundamental to showing the treatment’s efficacy. However, many questions about CAT remain unanswered. It is important to identify, for example, individuals particularly likely to benefit from CAT. It is also important to determine the extent to which measures of conditioned aversion to alcohol predict treatment outcome. 2. Subject jhctors

The notion that the treatment

of alcohol de-

pendent clients could be optimized by matching clients to appropriate treatments has recently been advocated (Miller and Hester, 1986c; Miller, 1989). The matching hypothesis is that clients assigned to particular treatments, on the basis of an appropriate matching strategy, will demonstrate treatment outcomes superior to those of clients who are mismatched or unmatched. Appropriate matching of clients to treatments requires knowledge of factors predictive of treatment outcome within respective treatment modalities. Few investigations have examined factors associated with treatment outcome within CAT programs and no studies have been conducted which employed a differential matching strategy (Miller and Hester, 1986c). Lemere and Voegtlin (1950) reported outcome data for 4096 of 4468 alcoholics treated between 1936 and 1950 with CAT. At follow-up, 60.5% of the patients were found to have remained abstinent for at least 1 year. Patients who were poor, under 25 years of age, with a history of employment difficulties, fared poorly following treatment relative to older, wealthier patients with stable job histories. This study produced l-year abstinence rates substantially higher than most previously reported. Thimann (1949b) reported outcome results of 245 patients treated at the Washingtonian Hospital, in Boston, between 1942 and 1949. Overall, 125 patients (51.02Yo) were abstinent for at least 1 year following treatment. Thirty patients were lost to follow-up and were not included in analyses and nine patients relapsed once, were retreated, and considered abstinent for reporting purposes. Several evaluations of the CAT program offered at the Raleigh Hills Hospital chain were conducted by Wiens (Wiens et al., 1976; Wiens and Menustik, 1983) Neubuerger (Neubuerger et al., 1980; Neubuerger et al., 1982) and colleagues. Wiens et al. (1976) found 63.5Yo of 261 patients treated in 1970 with CAT abstinent. at 1 year follow-up. These are particularly impressive data given that 92.5% of patients were successfully followed-up and that those lost to follow-up were considered relapsed. Wiens and

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Menustik (1983) reported that 243 (63.1%) and 252 (63.3%) of patients treated in 1978 and 1979, respectively, were abstinent at 1 year follow-up. Strong correlations between attendance of post-treatment ‘booster sessions’ and being married (for men) with treatment outcome were observed. Wiens and Menustik (1983) found that educational level, prior history of treatment and occupational and employment status were unrelated to treatment outcome while older patients fared better than younger patients following treatment. Nearly one-third of patients maintained abstinence for 3 years following treatment (1978: 31.2%; 1979: 35.2%). Neubuerger et al. (1980) attempted to crossvalidate Wiens’ et al. (1976) findings with a lower SES group of patients. For 275 subjects treated in 1975 and 290 treated in 1976, 33% and 43%, respectively, were totally abstinent for 1 year following treatment. Neubuerger et al. (1982) extended these findings to include outcome results of 277, 333, and 352 patients treated in 1977,1978, and 1979. All patients lost to follow-up were considered relapsed. One-year abstinence rates for these years were 54%, 49% and 54%. Like Lemere and Voegtlin (1950) and Wiens and Menustik (1983), Neubuerger et al. (1980) found demographic variables related to treatment outcome; for example, 73% of married and employed alcoholics treated between 1976 and 1979 maintained continuous abstinence for 1 year following treatment. Female patients, clients who were older, and patients not on Medicare, fared better than their respective counterparts. A number of investigations (e.g. Voegtlin and Broz, 1949; Neubuerger et al., 1982; Wiens and Menustik, 1983), have reported better results from chemical aversion therapy in alcoholics who are particularly heavy drinkers or severely dependent. Variables predictive of favorable treatment outcomes in chemical aversion therapy programs are similar to those predictive of outcome in other abstinence oriented treatments (Marlatt et al., 1988; Waisberg, 1990). At present, studies examining predictors of conditionability and treatment outcome in CAT programs are needed. This data would facilitate propitious patient-treatment

matching procedures. A final area of needed research concerns the extent to which alcohol dependent individuals find an arduous treatment regimen like CAT acceptable. 3. Magnitude

of conditioned

responding

and

treatment outcome

Cannon et al. (1986) found 27 of 60 (45%) subjects treated with CAT to be abstinent at 1 year follow-up. Results indicated that magnitude of conditioned aversion to alcohol influenced treatment outcome; heart-rate responses to alcohol at post-treatment significantly differentiated between continuously abstinent and relapsed patients at 1 year follow-up. Cardiac response (CR) to alcohol following CAT accounted for approximately 30% of the variance in latency to first drink among patients who relapsed following treatment. Noncardiac aversion measures, such as taste-test alcohol consumption or skin conductance response, were not predictive of outcome. Boland et al. (1978) found that eight of 25 patients treated with lithium CAT did not consistently become ill during conditioning trials. Only one (12.5%) patient in this group was continuously abstinent at 6 months follow-up, compared to 47.1% of the 17 patients who became consistently ill during CAT trials. investigations Uncontrolled methodological issues

4.

of

CA T:

The uncontrolled studies described above are, for various reasons, methodologically flawed. Lacking a control group, positive findings from these studies can be attributed to patient characteristics, other intervention components, and non-specific factors. This is especially the case, given that socioeconomic and drinking history variables are known to predict treatment outcome within CAT programs (e.g. Neubuerger et al., 1980) and across a variety of other alcoholism treatment modalities (Marlatt et al., 1988). Patients seeking treatment at private hospitals offering CAT probably have more favorable prognoses than alcoholics in public treatment programs. Nathan (1985) comments:

To begin with, patients entering chemical aversion programs (which are costly) must have substantial private financial resources, health insurance, or another source of third-party reimbursement; both of the first two funding sources would require patients to be either recently or still employed. Recent or current employment, in turn, suggests that the individual retains a modicum of ability to function adequately in the world. Further, many of these patients also differ markedly in educational and socioeconomic levels from alcoholics treated elsewhere, additional indications of their superior treatment potential. Finally, patients who complete a chemical aversion treatment sequence must be highly motivated to change their drinking behavior, since the treatment is both expensive and extremely unpleasant. It is given, of course, that positive treatment motivation is one of the most important

predictors

of successful

treatment.

(p. 362)

A recent report (Smith and Frawley, 1990) exemplifies the interpretative problems posed by uncontrolled studies of CAT. Two hundred patients treated with CAT were contacted 13 - 25 months (mean = 20.5 months) following treatment at a private hospital offering multifaceted alcohol treatment incorporating a CAT component. Outcome findings indicate that 62.6% of clients were continuously abstinent for 12 months following treatment. The treatment outcome figure reported by Smith and Frawley (1990) is virtually identical to the figures reported by Wiens and Menustik (1983). The methodology employed in both studies does not allow for an assessment of the independent contribution of each interventive component (e.g. counseling) to treatment outcome. Moreover, subject selection factors could feasibly explain these unusually favorable treatment findings. Smith and Frawley (1990) report that 79% of their sample was employed at pretreatment and that 65% had not been in treatment previously. Approximately 60% of patients were married and over half were employed as professionals or were in other white collar professions. Eighty percent of clients had 12 years or more of education. The sample studied by Smith and Frawley (1990) evidenced an unusual degree of social stability and accomplishment that may be reflected in the high rates of abstinence at 1 year follow-up. That is, it is possible that the ‘spontaneous remission’ rate for this socially advantaged

group at 1 year follow-up may approximate 60%. Research conducted by Bromet et al. (1977) suggests that clients in CAT programs are similar to clients in other private programs visa-vis demographic characteristics and quite unlike clients treated in public programs. Other methodological inadequacies of these studies include: (1) failure to validate patient self-reports of drinking status with information from collateral sources (Lemere and Voegtlin, 1950); (2) exclusion of patients lost to follow-up from statistical analysis, possibly inflating reported abstinence rates (Thimann, 1949a,b); (3) failure to conduct blind assessments of follow-up drinking status (Wiens et a1.,1976); (4) failure to report sample selection criteria and characteristics (Thimann, 1949a,b), (5) failure to objectively assess conditioned aversion to alcohol (Wiens and Menustik, 1983); and (6) failure to conceive of treatment outcome multidimensionally (Neubuerger et al., 1980, 1982). It is important to recognize that these methodological failings characterize the corpus of the alcohol dependence treatment outcome literature and are not unique to investigations of CAT (Miller and Hester, 198613). 5. Comparative

studies

In an early controlled investigation of CAT, Wallerstein (1956) evaluated the relative effectiveness of CAT (emetine). antabuse, hypand milieu therapy. Therapeutic notherapy, modalities were offered ‘side-by-side’ on the same ward to groups of clients sharing the same environment. Thus, the potential for contamination of treatment groups, through shared discussion, was high. Wallerstein (1956) found that 47 patients (8370) receiving antabuse completed treatment, compared to 50 (80%) 39 (64%), and 42 (62%) of CAT, hypnotherapy and milieu therapy subjects, Although respectively. Wallerstein reports that antabuse therapy was superior to the other three treatment groups these with respect to treatment outcome, results are compromised by the methodological problems noted above. In addition, random assignment procedures were violated, patient

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characteristics were confounded with treatment type, a high percentage of subjects was lost to follow-up and collateral validation of patients self-reports was not attempted. In addition, Wallerstein employed a ‘backward conditioning’ CAT protocol that was unlikely to produce conditioned aversion to alcohol. Jackson and Smith (1978) evaluated the effectiveness of the chemical and electrical aversion therapies offered at Schick Shade1 Hospital. All patients received a multimodal therapeutic regimen in addition to either type of aversion therapy. Two hundred eighty-seven patients received CAT and 57 received electrical aversion therapy. Patients received electrical aversion therapy only if it was determined that there were medical and/or psychological contraindications to CAT. Patients completing fewer than 3 of 5 scheduled aversion conditioning sessions were not included in the follow-up investigation. Fifty-five percent of CAT and 58% of electrical aversion patients returned questionnaires mailed to them. Fifty-seven percent of CAT and 55% of electrical aversion patients reported abstinence at 2 years follow-up. These data must be interpreted cautiously as patients were not randomly assigned to treatments, and may have been assigned to treatments on the basis of factors related to treatment outcome. In addition, the percentage of patients followed-up was low. The two best studies employing comparison groups are those reported by Boland et al. (1978) and Cannon et al. (1981). Boland et al. (1978) compared the effectiveness of titrated calcium carbimide (CCC), an antabuse-like agent, and CAT, using lithium carbonate as the aversive agent. Twenty-five consecutive admissions to a general hospital psychiatric ward received CAT. Six months following termination of the CAT program, another 25 consecutive admissions were treated with CCC. Subjects in this study had relatively poor prognoses (68% unemployed; 60% with prior admissions for alcoholism; 65% emergency, as opposed to elective admissions). At 6 months follow-up, 9 of 25 (36%) CAT subjects were abstinent compared to 3 of 25 (12?70) CCC subjects. Moreover, of the eight CAT patients who did not consistently become sick in

response to lithium during treatment, only 1 (12.5%) was continuously abstinent at 6 months follow-up. The abstinence rate at 6 months follow-up for the 17 patients who became sick more than once during CAT was 47.1%. Comparisons of the CCC and CAT samples on a number of dimensions yielded two significant findings. The CAT group was hospitalized a mean of 6 days longer than the CCC group and their mean age was 35.0 years compared to 40.0 years for the CCC group. One limitation of this study is the fact that the control group was not treated concurrently with the CAT group and staff expectations for the two groups, as well as historical influences, may not have been similar. In addition, there is no description of the followup assessment procedures. Were individuals conducting follow-up assessments blind to subjects’ group assignments? Finally, failure to assign subjects randomly to treatment conditions allows for the possibility that observed differences in treatment outcome are attributable to pretreatment differences between groups with respect to variables (e.g. age) predictive of outcome. The most sophisticated trial of CAT to date is reported by Cannon et al. (1981). They randomly assigned 20 subjects to one of three groups: (a) CAT (n = 7); (b) shock aversion therapy (n = 7); or to (c) a control group (n = 6). All subjects participated in a multifaceted inpatient alcoholism treatment program including group, individual, marital, and family therapy, assertion and relaxation training, Alcoholics Anonymous, sex education, vocational training and antabuse maintenance. At 6 months follow-up, CAT subjects were abstinent a mean of 170 days, while shock aversion therapy and control subjects were abstinent 109 and 158 days, respectively. Group comparisons revealed that CAT subjects were abstinent significantly more days than were patients in the combined shock aversioncontrol group. At 1 year follow-up, CAT subjects were abstinent a mean of 309 days, compared to 180 days for shock subjects and 304.8 days for controls. Both control and CAT groups displayed significantly greater numbers of days abstinent at 1 year follow-up than the shock

aversion group, but did not differ significantly from each other. The shock-control combined group did not significantly differ from the emetic group at 1 year follow-up. Twenty-nine percent (2 of 7) of CAT subjects and 17% (1 of 6) of control subjects remained continuously abstinent for 6 months following treatment. Interpretation of the Cannon et al. (1981) investigation is complicated by a number of factors. The foremost, is the small number of subjects assigned to each treatment group. The second factor, concerns the questionable analytic practice of comparing the treatment outcome of the emetic group with only that of the combined shock and control groups at 6 months followup. It is not clear why planned orthogonal contrasts did not include separate comparisons of the CAT group mean with the shock aversion and control group means. At both 6 months (170 vs. 158) and 1 year (309 vs. 304.8) follow-ups, it is difficult to evaluate the clinical significance of the difference between CAT and control groups with respect to number of days abstinent. It is important to stress that the Boland et al. (1978) and Cannon et al. (1981) studies may have underestimated the effectiveness of CAT. Boland et al. (1978) used lithium rather than emetine as the emetic agent. Eight of 25 patients in the Boland et al. (1978) study either failed to get sick or got sick only once. The relative effectiveness of lithium and emetine for use in CAT of alcohol dependence has not been established. In addition, Boland et al. (1978) did not employ ‘booster sessions’ during the followup period to promote longevity of the conditioned alcohol-aversion. Cannon et al. (1981) reported low rates of client participation in posttreatment booster sessions and used an emetic preparation that was medically more conservative, and potentially less effective, than those commonly employed in clinical trials of CAT (e.g. Wiens and Menustik, 1983). In addition, a ceiling effect may have been present in the Cannon et al. (1981) study due to the substantial number of post-treatment days abstinent for both control and CAT groups. Patients in all three treatment groups received an unusually comprehensive treatment package. Thus, the

CAT intervention was evaluated with respect to its incremental contribution to treatment outcome. These factors substantially reduced the probability of finding a clinically significant treatment effect. Thus, there is preliminary evidence suggesting that CAT procedures are effective vis-avis production of conditioned aversion to alcohol. However, with the exception of the investigations conducted by Cannon, Baker and colleagues, most evaluations of CAT have failed to assess domains of behavior likely to reflect conditioned alcohol aversion. For example, the extent to which CAT affects cognitions (e.g. positive outcome expectancies) related to drinking is unknown. In addition, research relating the magnitude of conditioned alcohol-aversion to treatment outcome is needed. The reports of Boland et al. (1978) Cannon et al. (1986) and Elkins (1980b) suggest that magnitude of conditioned aversion is predictive of treatment out,come. Additional research is needed to identify patients who are likely to benefit from CAT. CAT and alternative effectiveness

treatments:

differential

A number of investigators claim that applications of emetic aversion therapy are unethical because equally effective alternative treatments are available which are less intrusive and safer (e.g. Wilson, 1987). Several points should be made in regard to this contention. First, few studies have directly compared the effectiveness of CAT and other promising aversive (e.g. covert sensitization) and non-aversive treatment methods (Miller and Hester, 1980; Miller and Hester, 1986b). Second, while there is support for the efficacy of alcoholism treatment in general, there is little evidence documenting that one treatment modality is more effective than another, i.e. that there is one ‘best’ treat.ment (Emrick, 1974; 1975; Armor et al., 1978; Polich, Armor and Braiker, 1981; Saxe et al., 1983; Nathan and Skinstad, 1987). Third, evaluations of controlled research suggest that treatment outcomes do not significantly differ for clients assigned to either inpatient or outpa-

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tient treatment. In addition, length and intensity of treatment have not proven to be useful predictors of treatment outcome (Miller and Hester, 1986a). Fourth, although few attempts have been made to determine optimal patienttreatment matching strategies, certain clinical procedures appear to be differentially beneficial for specific types of clients (Miller and Hester, 1986b,c). In the case of CAT, Elkins (in press a,b) argues that patients who are middle-aged, nonmarried, employed or employable, psychopathic and reasonably well-adjusted, except for problems related to excessive drinking, have generally benefited most from CAT. Likewise, Nathan (1985) notes that CAT patients typically have better prognoses than patients entering other forms of treatment. Nathan (1985) contends that CAT produces treatment outcomes in a group of socially advantaged alcoholics superior to those produced by other treatment methods. Thus, the positive reports from uncontrolled investigations may reflect effects of patient by treatment type interactions as well as main effects for patient characteristics (e.g. being married) known to be predictive of treatment outcome. Fifth, while research to date has not identified a single best modality for the treatment of alcohol dependence, treatment procedures do differ in the extent to which their use is supported by their respective empirical databases. Treatment modalities for which there is little or no empirical support are alcoholism education, confrontation, group therapy, and individual counseling (Miller and Hester, 1986b). Some support for the application of disulfiram to selected alcoholic subgroups is provided by a recent multi-center evaluation (Fuller et al., 1986). These investigators report that among patients who drank following discharge those receiving 250 mg of disulfiram a day reported significantly fewer drinking days (49 + 8.4) than patients receiving 1 mg of disulfiram daily (108.7 + 14.7) or no disulfiram (116.4 f 16.3) at 1 year followup. The authors concluded that ‘the subset who benefited from disulfiram treatment were older and more socially stable than others who relaps-

ed.’ This subgroup of alcoholics is similar to the group that appears to benefit most from treatment with CAT. Because of its insistence on anonymity, support for AA has been difficult to obtain and an informed evaluation of the merits of AA awaits controlled experimental trials. Treatment modalities currently supported by controlled outcome research are aversion therapies, behavioral self-control training, community reinforcement approaches, marital and family therapy, social skills training, and stress management (Miller and Hester, 1980; Miller and Hester, 198613). In sum, the database pertaining to the comparative effectiveness of CAT and other treatment approaches is not sufficient to support an informed selection between promising modalities. CAT is one of a limited number of approaches that are empirically supported by controlled outcome research and there are preliminary indications of patient types likely to benefit from CAT. Given that no one approach to the treatment of alcoholism has gained preeminence on the basis of empirical findings, further research on CAT is justified by the fact that CAT may be more effective than other modalities with certain subpopulations of alcoholics. Moreover, the effectiveness of other promising treatment modalities may be enhanced by the addition of a CAT treatment component. Research identifying patients likely to benefit most from CAT should proceed apace. At present, CAT appears to be no less effective than the other promising approaches identified by Miller and Hester (1986b); yet, research to establish its efficacy with reasonable certainty remains to be done. Because of the intensity and intrusiveness of CAT, CAT may be limited, to some degree, in its acceptance by patients and professionals, and in the patient groups to which it will be applied. Increasingly rigorous medical diagnostic procedures and the use of oral, as opposed to intramuscular, emetine have made administration of CAT relatively safe. Future findings will clarify the limitations of CAT and will enable practitioners to identify

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clients likely to benefit most from this modality. Thus, we support continued investigation of the effectiveness of CAT. Summary Treatment of alcohol dependent persons with CAT dates back to the first century A.D., when Pliny the Elder listed a number of such techniques in his Historiales Naturalis (Thimann, 1949a). The historical origins of CAT within contemporary folk medicine (e.g., Daniels, 1982) are unknown. The earliest known case of CAT alcoholism treatment in the medical literature was reported in Colonial America by Rush (1815/1972). Systematic application of aversion therapy to the problem of alcohol dependence originated in the Soviet Union where Kantorovich (1930) developed an electrodermal conditioning treatment based on the work of the Russian physiologists Sechenov, Pavlov and Bechterev. The thrust of aversion therapy quickly shifted to CAT (Sluchevsky and Friken, 1933). CAT alcoholism treatment, which became a leading therapeutic strategy in the Soviet Union, soon spread to other countries. Alcoholism treatments involving CAT, which have been used in at least 75 settings in numerous countries since 1933, have generated more than 120 scientific reports (Elkins, in press a). The treatment has been in continuous use in several United States hospitals since the late 1930s. During the 1970s and early 198Os, CAT became more widely available in hospital settings (Wiens and Menustik, 1983). The number of facilities offering CAT has declined dramatically in recent years (Elkins, in press a). Emetic aversion interventions are based on the plethora of empirical findings derived from animal and human investigations of CA learning. Taste-aversion learning has been the most frequently studied variety of CA learning. The TA conditioning literature, constituting over 1300 reports in 1985 (Riley and Tuck, 1985), depicts TA acquisition as a phylogenetically old, exceptionally efficient, and ubiquitous form of learning (Elkins, 1989). One-trial learning is not

uncommon in TA conditioning (Elkins, 1973, 1984; Garb and Stunkard, 1974), and extended temporal intervals may separate presentation of the ingesta (CS) and subsequent illness (US) (Estcorn and Stephens, 1973; Logue, 1985). With use of repeated conditioning trials and discrimination training, aversions can be conditioned to highly familiar substances (Elkins, 1974) and are resistant to the processes of extinction and forgetting (Elkins, in press a). CAT protocols have been applied in diverse manners, but have rarely been evaluated with respect to the choice of pharmacological agent used to produce the US reaction. The three most widely used CAT conditioning agents are emetine, apomorphine, and disulfiram (Elkins, in press a). Conditioning involving the pairing of alcohol ingestion with disulfiram reaction fell into disfavor following a 1952 World Health Organization recommendation that emetine and apomorphine are more appropriate CAT agents (Glatt, 1962). Apomorphine was used in the United States only during the early phase of CAT development. Emetine has been the US drug of choice for CAT alcoholism treatments within the United States; more than 25 000 CAT patients have received this agent. The following conclusions can be drawn: (1) the human CAT literature indicates that emetine is the agent that most reliably produces nausea and emesis; (2) emetine is effective, vis-a-vis production of conditioned aversion and is relatively innocuous (Loomis et al., 1986); and (3) the follow-up abstinence rates that typically have been reported by the large United States treatment programs are among the highest to appear in the alcoholism treatment literature. Studies conducted by Cannon and associates (1979, 1981, 1986) provide psychophysiological, attitudinal, and behavioral evidence that conditioned aversion to alcohol is produced by CAT. The degree to which successful alcohol-aversion conditioning contributes to treatment outcome is not yet known. Studies conducted in the last decade (Boland et al., 1978; Cannon, Baker and Wehl, 1981) suggest the addition of a CAT component to a comprehensive and multifaceted

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treatment program may produce modest enhancements of treatment outcome. It is important to note that these studies, for a number detailed above, may have of reasons underestimated the effectiveness of CAT. Given the above mentioned findings vis-a-vis safety, ethics and efficacy, it is concluded that CAT research should proceed apace. Lithium appears to be a promising CAT agent. Agents producing noxious states other than nausea and vomiting, such as succinylcholine, nicotinic acid, and sulfadiazine, do not capitalize on the ‘biological preparedness’ of humans to form associations between ingestion of a consumable and subsequent nausea. Controlled trials have found succinylcholine ineffective. Succinylcholine induced apnea is ethically indefensible without informed consent. Given inthe treatment lacks a formed consent, compelling rationale. We are not aware of any controlled evaluations of sulfadiazine, lycopodium, or nicotinic acid. Apomorphine and ethanol have little support at the animal or human level as agents potentially superior to emetine or lithium for CAT. Non-pharmacologic means of nausea induction need to be compared with emetic aversion therapies with respect to the extent to which they produce conditioned alcohol-aversions and favorable treatment outcomes. In this vein, it is important to note that the promising findings of recent applications of covert sensitization to the treatment of alcohol dependence, may pose further limitations on the use of CAT. Recent applications of covert sensitization have demonstrated that the technique produces conditioned alcohol aversions in a sizable proportion of treated subjects, and that successful conditioning is predictive of treatment outcome (Elkins, 1980b; Miller and Dougher, 1984; Miller and Dougher, in press). Comparative evaluations of CAT and covert sensitization are warranted, given the greater intrusiveness and intensity of CAT. Potential patient/treatment matching variables should receive special attention within CAT/covert sensitization treatment outcome comparisons. The two treatments may prove to be maximally beneficial to different subsamples of the alcoholic population.

With respect to ethical considerations, it is concluded that current clinical applications of emetine based CAT with informed clients who deem the treatment to be appropriate to their objectives are morally defensible. This view is supported by evidence supporting the relative safety of oral emetine in the hands of skilled practitioners (Loomis et al., 1986) and by clinical evaluations of CAT suggesting that it is a promising treatment for alcohol dependence (Miller and Hester, 198613). Comparative evaluations of CAT and broad spectrum non-aversive treatment modalities are needed. Studies like these will yield important knowledge about the effectiveness of CAT and lead to a greater understanding of patient characteristics predictive of favorable treatment outcomes in CAT programs. Additional research evaluating issues relating to alcohol presentation during conditioning trials needs to be conducted. At present, it is recommended that clinicians ensure that presentation of alcohol precedes the onset of nausea. If oral emetine is used, alcohol consumption may begin concomitantly with or during the 5 min following administration of the agent. Current research findings suggest that patients receiving CAT should swallow a small amount (30 - 60 ml) of alcohol during conditioning trials as opposed to simple tasting of the beverage; consumption of voluminous quantities of ethanol is unnecessary and potentially dangerous. Little is known about the optimal temperature, dilution, and carbonation at which the alcohol (CS) should be presented. Additional methodological issues in CAT protocols requiring empirical evaluation include: (1) determination of the optimal number of CAT trials for a particular client; (2) determination of the point at which a client has had ‘enough’ conditioning within a given trial; and (3) determination of the conditioning and outcome effects of presenting one variety or several different types of alcoholic beverages during a single treatment session; and (4) determination of the optimal number and timing of postdischarge aversion reinforcement treatments. Exploration of various manners of delivering CAT should be initiated. It is important to know, for example,

whether CAT can be effectively administered to groups or via an indwelling pump or delivered in an outpatient setting. Chemical aversion treatment of alcohol dependence is a promising treatment for alcohol dependence. Randomized clinical trials of CAT are needed, especially those that assess the independent and incremental effects of jointly applied CAT and cognitive behavioral interventions. These studies will allow for more sophisticated evaluations of the efficacy of CAT. Acknowledgements

Grateful acknowledgements to Shirley Hansen for her help in the preparation of this manuscript and to Reid Hester, Ph.D., Jeffery M. Jenson, Ph.D. and P. Joseph Frawley, M.D., and to the four anonymous reviewers whose incisive comments were particularly appreciated. This research was supported in part by grant No. 65-0047 from the Alcohol and Drug Abuse Institute, University of Washington, Seattle, Washington. References Ajariaguerra. troubles

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