Dreams, Hallucinogenic Drug States, and Schizophrenia: A Psychological and Biological ... ·...

VOL 9, NO. 1, 1983 Dreams, HallucinogenicDrug States, andSchizophrenia: APsychological andBiological Comparison

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by Lawrence G. Flschman Abstract

Many observers have noted similari-ties between dreams, hallucinogenicdrug states, and schizophrenia. In thepresent article, certain fundamentalareas of convergence between thethree states are described. Considera-tion is given to the hallucinogenicdrug model of psychosis: the reasonsfor its initial attractiveness, and thereasons for its current disfavor. Theconcept of ego boundaries is defined,examined, and applied to the threestates. In these states, the ego's ca-pacity to average or synthesize vari-ous self-representations into a contin-uous, coherent self is compromised—leading to an impairment of the real-ity-oriented secondary process, andthe emergence of the florid attributesof the primary process. This can ac-count for many of the familiar char-acteristics of the three states. Currentneurophysiological theories of dreamand hallucinogenic drug states arepresented, with emphasis upon sero-tonin neurotransmission. Serotoninappears to play a prominent role inthe regulation of these states. The an-alogy contained in the present articlesuggests that serotonin may play arole in regulating schizophrenic statesas well.

The similarity between dreams andmadness has been noted frequentlythroughout recorded history, eversince phenomenological observationsto this effect were made by Aristotleand Plato (see review by Evarts1962). Kant stated, 'The lunatic is awakeful dreamer." Schopenhauerwrote, "A dream is a- short-lastingpsychosis, and a psychosis is a long-lasting dream."1 Freud simply re-

1 The translated quotations of Kant andSchopenhauer are from La Barre (1975,p. 12).

marked, "A dream, then, is a psy-chosis" (Freud 1940, p. 172).

In the mid-nineteenth century,Moreau (de Tours) added a new di-mension to this analogy. Moreau(1845) suggested that hashish-derivedhallucinations and mental illnesswere virtually identical psychicalstates resulting from cerebral excita-tion; that the ingestion of hashishbrings about a kind of "sleeplessdream" (p. 19). Moreau was thus thefirst to note the phenomenologicalsimilarities between the three statesof consciousness to be discussedhere: dreams, drug-induced states,and psychosis.

With Hoffman's (1979, p. 58) ser-endipitous discovery of the "dream-like" effects of D-lysergic acid diethy-lamide (LSD) a broad-based researcheffort was undertaken to elucidatethe biological and psychologicalmechanisms of hallucinogenic drugs,in the hope that such knowledgewould lead to an understanding ofthe basis of schizophrenia. In anotherarena, the discovery of rapid eyemovement (REM) sleep epochs (Aser-insky and Kleitman 1953) precipitat-ed an intensive investigation into thephysiology of sleep and dreams. Thepurpose of this article is to show thatrecent advances in the fields ofneurophysiology, psychopharmacol-ogy, ego psychology, and behaviorcan be related to the observations ofMoreau and others in demonstratingsimilarities between dreams, hallucin-ogenic drug states, and psychosis. Noclaim is made here for identity be-tween these states. The three statesshare several common properties, buteach of the three retains an identify-

Reprint requests should be sent to Dr.L.G. Fischman, Department of Psychiatry,Payne Whitney Clinic, The New YorkHospital-Cornell Medical Center, 525 East68th Street, New York, NY 10021.

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74 SCHIZOPHRENIA BULLETIN

ing set of features (Jacobs and Trul-son 1979a). These distinctive featuresshould not, however, be allowed todetract from the possible heuristicvalue that an analogy between thethree states might afford. In the fol-lowing pages, an attempt is made toadduce the basis for this analogy. Inso doing, a selected review of therelevant literature is cited.

A Chemical Psychosis?

Kraepelin was the first to attempt asystematic study of the phenomenol-ogy of mental illness by means ofchemically induced psychoses, but asKnauer and Maloney (1913) attest,the substances employed by Kraep-elin produced syndromes which borelittle resemblance to endogenous psy-chosis. Knauer and Maloney werethe first to utilize one of the sub-stances variously called "psychedel-ic," "hallucinogenic," or "psycho-tomimetic"—namely, mescaline—as amodel for insanity. Beringer (1927) iscredited with the application of theterm "model psychosis" to the mesca-line-lnduced state. His study was fol-lowed by those of Kluver (1928),Dejong (1930), Kretschmer (1934),Stockings (1940), and Mayer-Gross(1951) in various attempts to specifythe analogy of the mescaline-inducedstate to schizophrenia.

Rinkel and colleagues began hu-man experimentation with LSD in theUnited States in 1949. After a seriesof studies, they concluded that LSDwas "an excellent tool for the investi-gation of experimentally producedpsychotic-like manifestations" (Rinkelet al. 1955, p. 893). They also stated:

One cannot escape the impression,from these observations, that thesodo-psychological behaviorchanges showed similarities withthe general behavior of the mental-ly ill and that they provide funda-

mental implications in the field ofpsychotherapy, (p. 883]

The numerous studies alluded toabove helped form the thesis that thechemically induced psychosis result-ing from the administration of hallu-cinogenic agents was similar, if notaltogether identical, to the "natural-ly" occurring functional psychoses,particularly schizophrenia. Not unex-pectedly, what followed this wave ofinvestigation was its logical antithe-sis—that is, that the drug-inducedand schizophrenic states were mark-edly different, and could, in fact,easily be distinguished by profession-al observers (MacDonald and Galvin1956; Hollister 1962; Jacobsen 1963).Where Rinkel et al. (1952) had de-scribed similarities in "disturbancesof thought and speech; changes in af-fect and mood; perception; produc-tion of hallucinations and delusions;depersonalization and changes in be-havior" (p. 577), Hollister (1968)cited differences in the type of hallu-cination (mainly visual for drug-in-duced states, mainly auditory inschizophrenia); frequency of delu-sions (common among schizophren-ics, rare in drug-induced states); in-terpersonal relations (schizophrenicsare characteristically withdrawn,while subjects with drug-induced psy-choses prefer to have a companion);and speech (drug users' speech is "us-ually related to reality" while schizo-phrenic speech is "vague, ambiguousand difficult to follow") (p. 118).Since the two Hollister studies are byfar the most frequently cited ones indispute of the hallucinogenic drugmodel of psychosis, they bear closerscrutiny.

Hollister's (1968) findings coincidewith those of others (Feinberg 1962;Malitz, Wilkens, and Esecover 1962;West 1975) in citing a predominantlyvisual hallucinatory pattern in drugsubjects, as opposed to a primarily

auditory pattern among schizophren-ics. However, these observationswere based on comparisons usingchronic schizophrenic patients. Chap-man (1966) interviewed 40 youngschizophrenics (mean age •= 24.6years) with a recent onset of illness(average — 11 months' duration) anddiscovered that disturbances invisual perception, including halluci-nations, occurred with far greaterfrequency than disturbances in audi-tory perception. Young (1974) com-pared 20 recent onset schizophrenics(mean age — 19.5 years) with 20age-, sex-, and occupation-matched ,LSD subjects (and 20 matched con-trols). No significant differences werefound on five of seven measures ofvisual perception. Visual hallucina-tions occurred in 12/20 LSD subjectsand 9/20 schizophrenics. Young con-cluded that the two states are initial- -ly similar with regard to visual per-ceptual changes. A carefully con-trolled study by Freedman and Chap-man (1973) found more changes incategories of visual perception thanin auditory perception among "early"schizophrenics. McCabe et al. (1972)found that visual hallucinations oc-curred significantly more often in theacute than in the chronic schizo-phrenic state. Fischer (1972, p. 82)wrote:

the perceptual and especially visualexperiences of the incipient stagesof schizophrenia are not unlikethose induced by LSD or mescalineand auditory hallucinations onlybecome prevalent after the processhas lasted for some weeks ormonths.

Hoffer and Osmond (1960) suggestedthat visual perceptual disturbancesoccur with greater frequency inchronic schizophrenia than is general-ly reported, and that a gradual adap-tation to these takes place over time.Similar explanations have been of-

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fered by Landis (1964) and Winters(1975).

The contention that auditory hal-lucinations are more characteristic ofthe schizophrenic than of the hal-lucinogenic drug state fails to ac-knowledge the importance of socialand cultural factors (Al-Issa 1977).International studies of psychiatricpopulations have shown consistentlythat visual hallucinations are morecommon than auditory hallucinationsamong schizophrenics in the NearEast and in Africa (Murphy et al.1963; Jablensky and Sartorius 1975;Zarroug 1975). Cross-temporalstudies of hallucinations in Westernpatients suggest that only recentlyhas the frequency of auditory halluci-nations exceeded that of visual hal-lucinations (Opler 1956; Al-Issa1977). It is more prudent to assumethat sodocultural and methodologi-cal differences account for the widevariations in data than to assumethat the biological mechanism ofschizophrenia differs from year toyear, or from country to country.For the same reason, it is precipitousto label the LSD state a poor modelof schizophrenic psychosis becausenowadays more chronic schizophren-ics in the United States admit to hav-ing auditory hallucinations than vis-ual hallucinations. In this country,the term "drug culture" came to sig-nify the highly visible psychedelicphenomenon which took place duringthe 1960s. The term itself underscoresthe inseparability of cultural determi-nants from the hallucinatory experi-ence. When one compares a healthy,volunteer LSD subject who certainlyhas some sense of expectation—notto say hope—of short-lived changesin visual perception to a hospitalizedchronic schizophrenic who is notgiven an experimental drug and hasno reason to expect altered visualperception, it is hardly surprising

that an LSD subject will usually re-port more visual hallucinations (Win-ters 1975). Hoffer and Osmond(1966, p. 13) stated:

It is, in our view, quite mistakenlysupposed that visual changes arethe predominant perceptualanomalies in the LSD-25 experi-ence, and that such happenings arerare in schizophrenia. We considerthat neither of these propositions istrue. Nevertheless, they nave beenused to suggest that the LSD-25state is a poor model of schizo-phrenia.

Finally, in the only age-, sex-, andoccupation-matched controlled study,30 percent of LSD subjects and only5 percent of schizophrenics reportedauditory hallucinations (Young1974). The data can be summarizedwith a minimum of contradiction bystating that the relative frequency ofvisual and auditory perceptualchanges seen in chronic schizophreniain the United States today may differfrom that seen in hallucinogenic drugstates, but that the frequency of suchchanges in acute or incipient schizo-phrenia closely parallels that which isseen in the drug states. Moreover,subjective reports on the nature ofthese perceptual changes suggest fur-ther areas of convergence (Horowitz1964; Bowers and Freedman 1966;Grinspoon and Bakalar 1979). This isdemonstrated in the following first-person accounts (S ~ schizophrenic;D •• drug subject):

My senses seemed alive, they hitme harder. Things appeared dear-cut, I noticed things I had nevernoticed before. [Bowers 1968,p. 350] (S)

My senses became extremely acute.I could see an ant upon a tree at agreat distance away. I could hearthe whispering of my compan-ion . . . far off from me. [Mastersand Houston 1966, p. 153) (D)

I have noticed that noises all seemto be louder to me than they were

before. It's as if someone hadturned up the volume. . . . I no-ticed it with most backgroundnoises. [McGhie and Chapman1961, p. 105J (S)Sensations were acute. I heard,saw, felt, smelled, and tasted morefully than ever before. . . .[Masters and Houston 1966,p. 10] (D)Colors seem to be brighter now,almost as if they are luminous.When I look around me it's like aluminous painting. [McGhie andChapman 1961, p. 105] (S)

This "experience of heightenedawareness" (Bowers 1968, p. 350) iscommon to hallucinogenic drugstates and to acute psychosis. Phe-nomenological accounts supplementthe quantitative data mentaionedearlier, and support an analogy be-tween the two states.

Phenomenological accounts of pri-mary delusional experience revealfurther similarities between the twostates (Snyder 1974):

a sense of special significance be-gan to invest everything In theroom; objects which I would nor-mally accept as just being there be-gan to assume some strange impor-tance. [Osmond 1970, p. 24] (D)

I became interested in a wide as-sortment of people, events, placesand ideas which normally wouldmake no impression on me. Notknowing that I was ill, I made noattempt to understand what washappening, but felt that there wassome overwhelming significance inall this. . . . [MacDonald 1960,p. 218] (S)

This awareness of "significance"—theexperience of expanded relevance ormeaning—is the initial stage in thedevelopment of delusional thinking(Jaspers 1923; Lopez-Ibor 1974). Theprimary delusional experience is fun-damental to hallucinogenic drugstates and to incipient psychosis, anddearly precedes the development ofsystematized delusions (Bowers and

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Freedman 1966; Bowers 1968). Thegreater frequency of systematized de-lusions in chronic schizophrenia(Hollister 1968) is merely a functionof the duration of this altered experi-ence. Interestingly, systematized de-lusions are quite frequent amongchronic LSD users (Fisher 1968).

Withdrawal, as with systematizeddelusions, is a criterion which distin-guishes between acute and chronicpsychosis, but not between hallucino-genic drug states and acute endoge-nous psychosis. Many investigatorshave stated that schizophrenic with-drawal is a reflexive process in whichthe schizophrenic and those aroundhim react to those aspects of theschizophrenic experience which aregenerally regarded as primary (Sadler1953; Chapman 1966; Osmond 1969;Grinspoon and Bakalar 1979). Sever-al studies have found similar with-drawal patterns associated withchronic LSD abuse (Fisher 1968;Glass and Bowers 1970; Davison1975). Silverman (1969) states thatwithdrawal is characteristic of bothhallucinogenic drug states and schizo-phrenia, and occurs in response toearlier perceptual changes of the typediscussed above.

When LSD is ingested unwittingly,schizophrenic-like withdrawal ismore likely to ensue. The followingis a C.I.A. agent's report on the ef-fects of LSD administration to an un-aware colleague. The "subject" waseventually found crouched beneath ahighway overpass:

He reported afterwards that everyautomobile that came by was aterrible monster with fantasticeyes, out to get him personally.Each time a car passed, he wouldhuddle down against the parapetterribly frightened. It was a realhorror trip for him. I mean, it washours of agony. It was like adream that never stops—withsomeone chasing you. . . . It wasawfully hard to persuade him that

his friends were his friends at thatpoint. He was alone in the world,and everyone was hostile. He'd be-come a full-blown paranoid.[Marks 1979, p. 71]

This description of a terrified, with-drawn individual is typical of thereaction to unaware ingestion of LSD(Upton 1969; Marks 1979). In suchcases, the tremendous bias intro-duced by the voluntary administra-tion of a drug is eliminated. Such ex-amples afford a more natural com-parison with acute endogenous psy-chosis; they call attention to the in-advisability of distinguishing the twostates on the basis that chronicschizophrenics are more withdrawnthan voluntary drug subjects (Hollis-ter 1968).

Another reported difference be-tween hallucinogenic drug subjectsand schizophrenics is in the area ofspeech production. To quote Hollis-ter (1962, p. 82):

Both drug subjects and schizo-phrenics nave difficulty expressingthoughts. In the former it may takethe form of drunken ramblings, orwhen severe, incoherence, butwhat comes out is usually relatedto reality. Schizophrenic speech isoften vague, ambiguous and diffi-cult to follow. Weird symbolic rep-resentations abound, words maybe confused with the objects theyrepresent, and severe telescopingmay result in the word salad. Drugsubjects are usually greatly con-cerned about their failure to com-municate; schizophrenics are not.

It is proposed here that the character-istics ascribed to schizophrenicspeech pertain equally to drug sub-jects' speech, and vice-versa. Six outof seven psychiatry textbooks(Bleuler 1924, p. 376; Henry 1938;Henderson and Gillespie 1940,p. 212; Sadler 1953, p. 407; Noyesand Kolb 1958, p. 396; Freedman,Kaplan, and Sadock 1976, p. 441;Day and Semrad 1978, p. 212) pulled

randomly from the shelves of a medi-cal school library use the word "inco-herent" in reference to schizophrenicspeech. Referring to the language ofdrug subjects, Grinspoon and Baka-lar (1979) write, "words become con-fused with the qualities of the objectsthey designate" (p. 105) and "objectsbecome charged with symbolic mean-ings" (p. 105). Krippner (1970) notesthat hallucinogens may cause one to"effect a union between the word andits object" (p. 237). Snyder (1974, p.60) reports that chronic LSD usersare "out of touch with reality" andshow "vague" thought patterns,which would imply a close resem-blance to chronic schizophrenia ac-cording to Hollister's schema. Like-wise, one could label the speech ofLSD subjects "vague, ambiguous anddifficult to follow," as an exchangebetween two LSD subjects demon-strates:

The interchange consumed one-halfto three quarters of an hour, andwent approximately as follows:S-7: Smiles at S-8.S-8: Nods vigorously in

response.S-7: Slowly scratches his head.S-8: Waves one finger before his

nose.S-7: 'Tides."S-8: "Of course."S-7: Points a finger at S-8.S-8: Touches a finger to his

temple.S-7: "And the way7"S-8: "We try."S-7: "Holy waters."S-8: Makes some strange ap-

parent sign of benedictionover his own head and thenmakes the same sign towardS-7.

S-7: "Amen."S-8: "Amen." [Masters and

Houston 1966, p. 102]

The contention that drug subjects,unlike schizophrenics, are "greatlyconcerned about their failure to com-municate" pertains only to chronicschizophrenics. Chapman's (1966)

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study of recent onset schizophrenicsshowed them to be extremely con-cerned about their inability to com-municate. One may appreciate thatany psychological or physical lossbreeds more concern during the peri-od immediately following the lossthan during a period several years af-ter it is first experienced.

Another frequently cited "dif-ference" between the schizophrenicand hallucinogenic drug states is thatschizophrenics exhibit primarilydysphoric, anxiety-related affects,whereas drug subjects usually displayeuphoria (Young 1974). However,close phenomenological investigationreveals that the earliest affectivechanges in schizophrenia are oftenpleasurable and exhilarating (Chap-man 1966; Bowers 1968; Osmond1969; Docherty et al. 1978). Lintonand Langs (1962, 1964) used "em-pirical scale" questionnaires toanalyze the affective changes in LSDsubjects. They found that most sub-jects initially experienced elation, butthat this was followed by anxious-ness and dysphoria as subjects feltthat they were losing control overtheir thoughts. This progression ofaffective states parallels that which isobserved in incipient schizophrenia.

Each of the reported differences be-tween hallucinogenic drug states andendogenous psychosis examinedabove has been found to reflect asimilarity between the two states.Mogar (1970) observed that no singlefeature or combination of featureshas been found to differentiate thetwo states. Hollister (1962, 1968)rightly argued that one should con-sider each state as a whole in orderto make meaningful comparisons.Hollister's (1962) study, in whichtape recordings of schizophrenics anddrug subjects were played before"blind" health professionals whowere asked to distinguish them, is

considered by many as proof that thetwo states have little resemblance.The study was beset by a number ofproblems, however. Foremost is thefact that chronic schizophrenics wereused; for the reasons cited above,such a comparison is of limitedvalue. In designing the study,Hollister cited "the differences inmany particulars" (p. 80) betweenthe states, and edited the tapes to in-clude sections "illustrating somecharacteristic aspects of either schizo-phrenia or the three drug states"(p. 85). Thus the tapes were arbi-trarily selected and edited to demon-strate characteristics that the authorfelt were distinctive of either onestate or the other, but not commonto both states. This introduces a tre-mendous degree of • vestigator bias.There were further problems, as theinvestigator stated:

Promptly it became apparent thatthe technique did not allow forcomplete blindness: drug subjectstalked mainly in the present tense,schizophrenics in the past; drugsubjects betrayed by accent anddiction a generally higher level ofeducation and social function thanschizophrenics. For these reasons,specific instructions were given theraters to rate the interviews onlyon content, even if they had reasonto believe the rating was actuallyin error. [Hollister 1962, pp.85-86]

As Denber (1962, p. 91) comments inhis discussion of this study,"[Hollister's] statement reminded meof the judge telling the jury, after theprosecutor had made a telling point,to strike that mark from the record.Obviously it is impossible, once theraters know something about it, tosay that we shall disregard thosethings." Furthermore, some author-ities believe that the drug doses thatwere used may have been too low(Grinspoon and Bakalar 1979). De-

spite these difficulties, authors whodiscount the hallucinogenic drugmodel of psychosis most often citethis study (and Hollister 1968) asconvincing evidence of the model'sshortcomings. In contrast, Hoffer(1956) taped verbatim interviewswith an LSD subject and an acuteschizophrenic. The recordings werethen played before a group of ex-perienced psychiatrists who were un-able to distinguish the patient fromthe drug subject. Ironically, manyyears after his original studies, Hol-lister reevaluated his position. Incomparing new onset schizophreniato the LSD state, he acknowledged "agreater resemblance than was former-ly thought" (Hollister 1978, p. 416).

It would seem, then, that the caseagainst the hallucinogenic drugmodel of psychosis has several weak-nesses. The argument for an analogybetween the two states must demon-strate that they share certain funda-mental properties. In the followingpages, consideration is given to thesefundamental properties, and theanalogy is expanded to includedream states.

Ego Boundaries

Savage (1955) traced all of the phe-nomena experienced within the LSDstate to a primary loss or decathexisof the ego boundaries, a concept de-rived from Federn (1952). Freeman,Cameron, and McGhie (1958) con-sidered the decathexis of the egoboundaries to be the fundamentaldisturbance from which all othermanifestations of schizophrenia fol-lowed. Fliess (1973) viewed the de-cathexis of the ego boundaries as thenecessary condition for hallucinatorywish fulfillment in dreams.

To understand what is meant bythe term "ego boundaries," one must

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review Federn's original concept andthe subsequent revision and inter-pretation it has undergone in theliterature. Federn used the term todenote a dynamic set of temporo-spatial limits which divide experienceinto past, present, and future; inter-nal and external; real and unreal. ForFedern, the ego presented a uniqueparadox because it is normally ex-perienced as both subject and objectat once. Jacobson (1954, p. 520),using Hartmann's (1950) distinctionbetween "ego" and "self," noted thatFedern's subject and object com-ponents of the ego corresponded tothe "system ego" and the "self-representation," respectively. Federn's"ego boundary" is identical with theboundary between self-representationand object-representation (Jacobson1954).

From clinical observation, Federnnoted that in incipient psychosis or,in healthy persons, upon fallingasleep, the ego (self-representation)boundaries lose their cathexis. En-larging upon Federn's observations,Spiegel (1959) wrote that the accurateperception of reality depends uponthe ego's continuous averaging ofself-representations to form a con-stant frame of reference: the self.The regressive loss of this averagedself-representation in dreams andpsychosis leads to a chaotic conditionin which various ego states succeedone another without a common refer-ence point. This renders a loss oftemporal continuity to experience.The hypnogogic phenomena de-scribed by Isakower (1938) are proto-typical of such experience. Moreover,internal processes can no longer bedistinguished from external ones.Sensory phenomena strike the weak-ened ego boundaries with unac-customed impact; colors and soundsare imagined as having increasedintensity. The distinction between self

and nonself is blurred. In this state ofaltered temporal and spatial relation-ships, the notion of causality is sec-ondarily affected. Thelmar (1937,p. 253) stated, commenting on herown psychosis, 'lunatics do not 'losetheir reason': they merely reasonfrom false premises."

While Federn's observations of thisphenomenon were confined to schizo-phrenic and dream states, othershave described a similar process inhallucinogenic drug states (Lintonand Langs 1962; Cohen 1964; Barr etal. 1972). Sarlin (1962) consideredthe withdrawal of cathexis from theself-representation to be the basis fordepersonalized states in general. Thefollowing accounts typify the kind ofprimary experience which suchformulations attempt to reconstruct:

I became aware of the body thatencased me as being very heavyand amorphous. Inside it, every-thing was stirring and seemed tobe drawing me inward. [Mastersand Houston 1966, pp. 9-10] (D)I feel as though I'm not alive—asthough my body is an empty, life-less shell. I seem to be standingapart from the rest of the world.[Bockner 1949, p. 969] (S)

The decathexis of the self-representation in dreams, hallucino-genic drug states, and acute psy-chosis results in a dichotomous expe-rience characterized by a weakeningof the ego's identification with theself. The ego, the structure to whichwe attribute the function of percep-tion, including perception of the self(Hartmann 1950), only partially andimperfectly perceives a relation to theself. Writers have used a variety ofterms to describe this dichotomy.Kleinman, Gillin, and Wyatt (1977,p. 573) describe LSD subjects andschizophrenics who experience a"separation of body and soul." Oneof Klee's (1963, p. 463) LSD subjects

states, "I feel like I'm a bystanderwatching myself." Jacobson (1959,p. 608) wrote that the depersonalizedstate which often heralds an acuteschizophrenic psychosis results froma "schism" in the ego. Linton andLangs (1964, p. 480) reported fortheir LSD subjects that "the ob-serving self became dissociated fromthe experiencing self." Stamm (1962)and Arlow (1966) observed that thisdissociation comprised the basis ofdepersonalized states; the latterauthor emphasized its occurrence indreams. Laing (1965, p. 71) men-tioned "a divorce of self from body"in describing the schizophrenic exist-ence.

What links these various charac-terizations is that each describes anestrangement of the "participating"self from the "observing" or per-ceiving agent. This estrangement isthe essential or enabling mechanismin the everyday occurrence of day-dreams and transient depersonaliza-tions. It consists initially in a disrup-tion of the ego's ongoing synthesis ofthe various self-representations into acontinuous, coherent self. A sus-tained disruption compromises theego's perception of the relationshipsbetween individual self-representa-tions. Eventually, the connectionsmay be lost; the ego may identifywith one or another self-representa-tion, but can no longer identify witha continuous, coherent self. It is tothis process that Federn loosely refersin describing a decathexis of the egoboundaries. This estrangement is thefundamental process which is seenalike in dreams, hallucinogenic drugstates, and acute psychosis. Its rela-tion to the loss of reality testing andthe emergence of the primary processin these three states can now be madeclear.

Freud (1917, p. 231) noted "thegreat practical importance of dis-

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tinguishing perceptions from ideas,however intensely recalled. Ourwhole relation to the external world,to reality, depends on our ability todo so." Rapaport (1951) recognizedthat the discrimination between ideaand perception depends upon one'scapacity for "reflective awareness,"which he defined as follows:

It seems to be a sub-species of thefunction that distinguishes imageryfrom hallucination and percept,thought from reality. The follow-ing are some form-variables ofreflective awareness: ideationwithout specific awareness, ide-ation with awareness, awarenesswith awareness that one is aware,etc. [p. 302]

Schafer (1968, p. 91) enlarged uponthis reasoning. He stated that realitytesting requires an ability to repre-sent "oneself as thinker of thethought—what shall henceforth becalled the reflective self representa-tion" (author's italics). Schafer ar-gued that the suspension of reflectiveself-representation enables the turn-ing away from reality in dreams andpsychosis. Moreover, he surmisedthat this is what Freud (1938, p. 276)alluded to in describing the "splittingof the ego" which occurs in thesestates. Thus Schafer relates the lossof reality in dreams and psychosis tothe dichofomous experience describedabove. Reflective awareness, orreflective self-representation, requirescomplete identification between theperceiving agent ("thinker of thethought") and the participating self.In dreams, hallucinogenic drugstates, and psychosis the participat-ing self is represented as a series ofdiscontinuous selves or parts ofselves. Reflective self-representationis suspended; reality is lost. Withoutthe coherent organization of variousself-representations into a continuousself, the secondary process is im-

paired, and the primary process pre-dominates.

Noy (1969) observed that the sec-ondary process depends upon: (1)the capacity to maintain a constantinner representation of the self and ofobjects; (2) the capacity to distin-guish between self and object andthus between internal and externalphenomena; (3) the capacity to shiftfrom "thing-presentation" to "word-presentation." We have seen that theability to meet the first two criteria isimpaired in the three states underconsideration. We may now callattention to the third criterion.

Freud (1917) elaborated on themechanism by which primary processtransformations occur in dreams:

In this process thoughts are trans-formed into images, mainly of avisual sort; that is to say, word-'presentations are taken back to thething-presentations which cor-respond to them. . . . The pri-mary psychical process is broughtto bear on these memories, till, bycondensation of them and displace-ment between their respectivecathexes, it has shaped the mani-fest dream content, [p. 228]

Arieti (1955, p. 244) has observedthis process, which he calls "per-ceptualization of the concept," in theevolution of schizophrenic hallucina-tion. Klee (1963, p. 467) noted the"visual, hallucinatory quality" of thethought of LSD subjects. Both Arieti,in describing schizophrenics, andKlee, in describing LSD subjects, re-late this regressive transformation to •the "concrete attitude" described byGoldstein (1944). Goldstein definedthe concrete attitude as one in whichthe subject is unable to transcend theimmediate sensory impressions im-parted by the environment and pro-ceed to the level of conceptual think-ing and abstraction. From similarobservations, Salzinger (1971) de-veloped an "immediacy hypothesis"

which seeks to explain schizophrenicsymptomatology by this phe-nomenon. Hartocollis (1980, p. 862)wrote, "In a dream everything is ex-perienced much more immediatelythan in awakeful reality." Concern-ing LSD subjects, Klee (1963, p. 469)wrote, "The relationship to objects,including people, takes on an un-usual quality and depth and an im-mediacy which dissolves the ordinaryexperience of continuity frommoment to moment." It is this qual-ity of vivid, immediate sense-imagerywhich characterizes the primaryprocess. Its presence signifies animpairment of the secondary processand a regressive transformation froma word-presentation to a thing-presentation mode of thought.

Freud (1900, p. 295; 1915, p. 199)observed that in dreams and inschizophrenia words undergocondensation and displacement viathe primary process; this producesthe neologisms and other transforma-tions which characterize schizo-phrenic speech. The same trans-formations have been observed inLSD states (Savage and Cholden1956; Klee 1963; Grinspoon andBakalar 1979). Fliess (1953) observedthat the dreamer treats verbal resi-dues in the manner of a schizo-phrenic—words are not conceived assymbols of objects, but as objectsthemselves. Identical observationshave been made regarding the hal-lucinogenic drug state (Krippner1970; Grinspoon and Bakalar 1979)and schizophrenia (Hollister 1968).Fisher (1954) concluded from histachistoscope experiments that indreams visual percepts are treatedconcretely as objects, and as such,are subjected to the transformationsof the primary process in much thesame way that Freud described forverbal residues. The theme echoed byall of these writers is that in all three

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states the net effect of these trans-formations is a tendency toward con-cretization. Rivers (1923) and Silberer(1909) have observed this tendency indreams and hypnogogic states, re-spectively. McGhie and Chapman(1961) and Weckowicz, Somner, andHall (1958) documented the sametendency in schizophrenics. DeShon,Rinkel, and Solomon (1952) andSilverstein and Klee (1958) noteddeficits in abstract thinking onproverb tests given to LSD subjects.

McKellar (1957, 1963) explainedthe loss of abstract thinking inschizophrenia, dreams, and mescalinestates as the result of an inability "toinhibit associated but irrelevantideas" (1957, p. 104). Conversely,Arieti (1955) 9aw the concrete atti-tude as the basis for the associationaldisturbance in schizophrenia. Manywriters in the schizophrenia literaturehave emphasized the associational orattentional disorder in their respec-tive theories of the disease (Bleuler1911; Cameron 1944; McGhie andChapman 1961). Venables (1964) em-ployed the term "input dysfunction"in an attempt to unify these relatedconcepts of schizophrenia.

Much research in the last twodecades has been devoted to thestudy of psychophysiological para-digms of this input dysfunction.Claridge (1978) found a strong simi-larity between acute schizophrenicsand LSD subjects on measures ofelectrodermal sensitivity and two-flash thresholds. Silverman (1968,1969) reviewed the literature on vari-ous laboratory measures of sensoryresponsiveness in LSD subjects andschizophrenics. He related the resultsof these psychophysiological studiesto reports of the subjective experienceof these states, which suggest that aheightening of sensory awarenesstakes place:

These studies are consistent with

the subjective report literature;they indicate that during a schizo-phrenic reaction and under the in-fluence of psychedelic drugs, (1)ordinary-intensity stimuli are ex-perienced more intensely than nor-mally/ and (2) less sensory infor-mation is necessary in order to re-fiort that a stimulus is present.Silverman 1969, p. 198]

A one-time schizophrenic patient de-scribed her first-hand experience ofthe "input dysfunction":

the mind must have a filter whichfunctions without our consciousthought, sorting stimuli and al-lowing only those which are rele-vant to the situation in hand todisturb consciousness. . . . Whathad happened to me . . . was abreakdown in the filter and ahodge-podge of unrelated stimuliwere distracting me from thethings which should have had myundivided attention. . . . By thetime I was admitted to the hospitalI had reached a stage of "wakeful-ness" when the brilliance of lighton a window sill or the color ofblue in the sky would be so im-portant it could make me cry. Ihad very little ability to sort therelevant from the irrelevant. Thefilter had broken down. Complete-ly unrelated events became intri-cately connected in my mind.[MacDonald 1960, pp. 218-219]

The passage simultaneously il-lustrates the interrelatedness of theinput dysfunction, heightened sen-sory awareness, and the primarydelusional experience in schizo-phrenia.

Terms like "input dysfunction,""immediacy hypothesis," and "con-crete attitude" designate qualities thatreflect the operation of the primaryprocess. Earlier it was argued thatthe impairment of the reality-orientedsecondary process is related to adisruption in the ego's normally con-tinuous and implicit identificationwith the self. The impairment of thesecondary process enables the emer-gence of the florid characteristics of

the primary process. Thus, many ofthe well-described traits of dreams,hallucinogenic drug states, and acuteschizophrenia can be related to whathas been called a decathexis of theself-boundaries, or more specifically,to a disruption of the ego's ongoingsynthesis of self-representations intoa continuous, coherent self. Thisrelationship can be partly explainedby, and readily seen, in discussingthe altered experience of time that oc-curs in the three states (MacKenzie1965).

Speaking of dreams and psychosis,Freud (1900, p. 91) wrote, "In boththere is a complete lack of sense oftime." Review of the literature on thesense of time in schizophrenia andhallucinogenic drug states revealsconsistent subjective reports of "time-lessness," time "standing still," ortime "slowed down" (Schilder 1936;Scott 1948; Savage 1955; Klee 1963;Hartocollis 1975; Grinspoon andBakalar 1979). Hartocollis (1980,p. 863) wrote, "The dreamer's tem-poral orientation is strictly in thepresent. . . ." Arieti (1955, p. 240)wrote of the schizophrenic, "Thetemporal orientation of the patientbecomes gradually limited to thepresent time." Anderson and Rawns-ley (1954, p. 47) found that LSD pro-duced "a sense of temporal insularityin which only the present was real,past and future being exceedingly re-mote." As Arieti (1955) points out,all thinking occurs in the presenttense. When one thinks about thepast or the future, the actualthoughts take place in the here-and-now. To differentiate memories andexpectations from present events, onemust appreciate the relationship be-tween the self-representation as-sociated with the memory or expecta-tion, and the self-representation as-sociated with the present thought. Ifthis relationship is not appreciated,

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the distinction between past, present,and future dissolves. In dreams, hal-lucinogenic drug states, and psy-chosis, the normal continuity ofexperience is disrupted. The ego per-ceives a number of disparate self-representations in lieu of a con-tinuous self. At first the relationshipamong these self-representations isuncertain. Eventually, no meaningfulrelationship is perceived. Orderedexistence is replaced by a sense oftimelessness; past, present, andfuture are as one.

I don't feel things are ordered. Ihave lost the sequence of events.[Rosser 1979, p. 183] (S)

I was not experiencing events inthe normal sequence of time. I wasexperiencing the events of 3.30[P.M.] before the events of 3.0; theevents of 2.0 after the events of2.45, and so on. [Mayhew 1956,pp. 294-295] (D)

Biological Considerations

It will be noted that the quotationsgiven in the introduction to this arti-cle emphasized the connection be-tween dreams and endogenous psy-chosis. The subsequent section wasprincipally concerned with theanalogy between endogenous anddrug-induced psychosis, though theanalogy was extended to dreamswhere appropriate. The final sectionemphasizes the biochemical, ana-tomical, and neurophysiological cor-relates of the analogy betweendreams and hallucinogenic drugstates.

Aserinsky and Kleitman (1953) dis-covered the existence of a regularperiodicity within sleep. Because ofthe regular occurrence of episodeswhich featured rapid eye movementsat approximately 90-minute intervals,the term REM sleep was coined.When subjects were awakened duringREM sleep, dream recall occurred

with much greater frequency thanwhen subjects were awakened atother times, termed non-REM(NREM) sleep. These results werereproduced by several investigators(Dement and Kleitman 1957; Good-enough et al. 1965; Stoyva andKamiya 1968; Feinberg 1970; Snyder1971). The studies showed thatdreams which occurred during REMsleep were characterized as beingvivid, intense, affectively charged,and filled with bizarre imagery of apredominantly visual nature. Dreamswere occasionally recalled fromNREM sleep awakenings. These weredescribed as "being more con-temporary and more thought-like incharacter than the narratives elicitedfrom REM sleep" (Feinberg 1970, p.126). Based on the preceding discus-sion, it seems that REM sleep dreamsreflect the active primary process anda regression to the perceptual modeof psychic function, whereas thedreams of NREM sleep displaycharacteristics intermediate to thoseof REM sleep and waking life; theyreflect an impaired secondary processwithout the florid attributes of thepure primary process.

Intensive investigation into thephysiological correlates of REM andNREM sleep led to the monoaminetheory of sleep states introduced byJouvet (1969, 1972, 1974). Brieflystated, this theory implicated theserotonergic neurons of the raphesystem—extending rostrally in themidline from the caudal medulla tothe caudal mesencephalon (Anden etal. 1965, 1966a; Dahlstrom and Fuxe1964, 1965; Fuxe 1965)—in themechanisms of NREM sleep as wellas in the "priming" of REM sleep(Jouvet 1972). It was postulated thatnoradrenergic fibers of the locusceruleus, a structure located in thelateral part of the brainstem teg-mentum (Dahlstrom et al. 1964;

Anden et al. 1966a, 1966k), were re-sponsible for the "executivemechanisms" of REM sleep Qouvet,1972). The theory was based onlesion experiments and neuropharma-cological manipulations in the cat.The advent of intraneuronal micro-electrode recording techniquesbrought about a substantial revisionof this theory. It has become possibleto monitor the firing rates of neuronsof the raphe system (particularlythose within the dorsal raphe nu-cleus, the most rostral member of theraphe system) as well as other brainsites, including the locus ceruleus. Bythis technique, one can estimate theactivity of these neuronal groupsthroughout waking and sleepingstates. Such studies have shown thatunit activity of cat dorsal rapheneurons undergoes a substantialreduction as the animal enters NREMsleep from the waking state(McGinty and Harper 1976; Trulsonand Jacobs 1979d). A further reduc-tion in firing rate occurs when theanimal goes from NREM to REMsleep. Thus there is a progressivediminution of serotonergic outflowfrom the dorsal raphe nucleus as theanimal progresses from the wakingstate through NREM sleep into REMsleep. During REM sleep these sero-tonergic neurons are virtually silent(Trulson and Jacobs 1979b; Sakaiand Jouvet 1980). A similar, but lesspronounced pattern of unit activityhas been observed for the norepine-phrine-containing neurons of thelocus ceruleus (Hobson, McCarley,and Wyzinski 1975).

These observations correlate wellwith pharmacological findings.Numerous drugs cause decreases inthe ratio of REM sleep to total sleeptime, but very few can effect an in-crease in this ratio (Jacobs 1978). Re-serpine depletes intraneuronal storesof serotonin as well as catechola-

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mines. Several studies have shownthat reserpine causes an increase inREM sleep time in man (Tissot 1965;Hartmann 1966; Hoffman andDomino 1969; Coulter, Lester, andWilliams 1971) and in other animals(Kkazan and Sawyer 1964; Reite etal. 1969; Stern and Morgane 1973).This is precisely what one would pre-dict based upon the findings of theintracellular recording studies; re-duced neurotransmitter contentwithin monoaminergic neurons is thehypothesized behavioral equivalentof diminished firing rates. Converse-ly, an increase in available neuro-transmitter should be the behavioralequivalent of an increased firing rate.Monoamine oxidase inhibitors(MAOIs) and tricyclic antidepres-sants are thought to act by increasingthe synaptic availability of serotoninand catecholamines. It has beenshown that MAOIs consistently sup-press REM sleep time in man (Wyattet al. 1971a, 1971b; Wyatt 1972).MAOIs may have a more pro-nounced effect on serotonin than onnorepinephrine levels (Pscheidt 1964;Sourkes 1972). In the cat, MAOIsselectively increase brain serotoninlevels without exerting significant ef-fects on other neurotransmitter sys-tems (Pscheidt, Morpurgo, and Him-wich 1964). A complete abolition ofREM sleep occurs when MAOIs areadministered to cats (Jouvet 1967).These studies suggest that the REMsleep suppressing effect of MAOIs isprimarily due to their effect uponserotonergic neurotransmission.

The results obtained with tricyclicantidepressants support the notionthat REM sleep depends on theactivation state of serotonin-contain-ing neurons. Dunleavy et al. (1972)administered six different compoundswithin this pharmacological class tonormal volunteers over a 4-weekperiod. Each drug suppressed REM

sleep time to varying degrees. Par-ticularly germane to the present hy-pothesis is that chlorimipramine,which is a strong serotonin reuptakeblocker but only a weak norepine-phrine reuptake blocker (Carlsson etal. 1969a, 1969b), was found to bethe most potent inhibitor of REMsleep (Dunleavy et al. 1972). Thisfinding has recently been duplicated(Leckman et al. 1980). Chlorimi-pramine is also the only tricyclicantidepressant that has been shownto produce profound REM sleep sup-pression in depressed patients (Pas-souant, Cadilhac, and Billiard 1975).

The ability of chlorimipramine tosuppress REM sleep is thought toconstitute the basis for its effective-ness in the pharmacological treat-ment of narcolepsy (Mendelson, Gil-lin, and Wyatt 1977; Chen 1980).Narcolepsy is considered to be a dis-order of the mechanism that controlsREM sleep (Rechtschaffen andDement 1969). The frequent occur-rence of hypnogogic (and hyp-nopompic) hallucinations is a promi-nent symptom of this disorder.Shapiro (1975) found that chlorimi-pramine therapy can alleviate thesesymptoms in narcoleptic patientswithin 48 hours. It is interesting toconsider these findings in the light ofFedern's (1952) observations on hyp-nogogic hallucinations. It will be re-called that Federn attributed this phe-nomenon to a withdrawal of cathexisfrom the ego boundaries. Drugswhich prevent the occurrence of hyp-nogogic hallucinations must (if oneaccepts Federn's observation) some-how be able to counteract this with-drawal. In this respect, one notesthat chlorimipramine was found tobe more effective than imipramine inthe treatment of narcolepsy, pre-sumably because of the chlorimi-pramine's greater relative potency atserotonergic synapses (Guilleminault,

Carskadon, and Dement 1974). Thisfinding fits nicely with the aforemen-tioned work with MAOIs in man andin the cat in implicating serotonergicsystems in the regulation of REMsleep. To return again to Federn'sconceptualization, it is as though theneurochemical analogue of the egoboundary cathexis is serotonergicoutflow. When this outflow is di-minished, as in REM sleep, a with-drawal of ego boundary cathexis alsooccurs. When this outflow is bol-stered by the administration of tri-cyclic antidepressants or MAOIs, thehypnogogic hallucinations of nar-colepsy are eliminated and REMsleep is suppressed. While this ob-viously simplistic analogy conformswell with the original Freudian modelof neuronal cathexis (Freud 1895), itis offered here merely to suggest anintriguing parallel. As will be seenhowever, this parallel fits nicely withother findings, and may haveimplications in the treatment ofschizophrenia which, as noted ear-lier, is believed by some investigatorsto result from a withdrawal of egoboundary cathexis (Freeman,Cameron, and McGhie 1958).

Wooley and Shaw (1954), notingthe structural similarity of the LSDand serotonin molecules, postulatedthat a blockade of central serotoninreceptors might account for LSD'spsychotomimetic effects. They pro-posed, in effect, a serotonin hy-pothesis of schizophrenia, which heldthat interference with' normalserotonergic neurotransmission mightresult in a schizophrenic psychosis.This hypothesis eventually fell intodisfavor for reasons to be consideredbelow. It did, however, succeed inprompting an investigation into theeffects of LSD on brain serotoninmetabolism. Rosecrans, Lovell, andFreedman (1967) found that LSDcaused a decrease in rat brain

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serotonin turnover. Aghajanian,Foote, and Sheard (1968) used anintraneuronal recording technique todemonstrate that intravenous orintraperitoneal administration of LSDto rats resulted in a sharply reducedfiring rate in neurons of the midbrainraphe nuclei, but not in neurons out-side of the midbrain raphe. Theseraphe neurons were identical with theserotonin-containing neurons de-scribed by Dahlstrom and Fuxe(1964, 1965). Further experiments re-vealed that this reduction in unitactivity was due to a direct effect ofLSD on the cell bodies of theseneurons (Haigler and Aghajanian1973). It was shown that 2-bromo-LSD, a congener of LSD without hal-lucinogenic properties, was much lesseffective than LSD in inhibiting unitactivity of dorsal raphe neurons, andcould not produce complete inhibi-tion even when administered in ex-tremely high doses (Aghajanian,Foote, and Sheard 1970). This resultcoincided with earlier findings that 2-bromo-LSD did not affect centralserotonin metabolism even whengiven in significantly higher dosesthan those at which LSD decreasedcentral serotonin turnover (Freedman1961; Rosecrans, Lovell, and Freed-man 1967). Since LSD and2-bromo-LSD are equipotent inperipheral serotonergic systems, thisraised the possibility that the uniqueinhibitory effect of LSD upon the dis-charge rate of dorsal raphe neuronsmight account for its hallucinogenicproperties.

This latter possibility received sup-port from the finding that LSD,psilocin, 2,5-dimethoxy-4-methyl-amphetamine (DOM), N,N-dimethyltryptamine (DMT), mes-caline, and 5-methoxy-DMT, whichhave similar if not identical psy-chological effects and which show ahigh degree of cross-tolerance with

each other (Jacobs and Trulson1979a), all exert a marked inhibitoryeffect upon dorsal raphe neurons(Aghajanian, Foote, and Sheard1970; Aghajanian and Haigler 1975;Mosko and Jacobs 1977; Jacobs1978). Moreover, the relative po-tency of these hallucinogenic drugs indepressing the discharge rate of theseneurons corresponds to their relativepotency in various psychological andperceptual measures in man(Wolbach, Miner, and Isbell 1962;Snyder, Faillace, and Hollister 1967;Szara 1970; Trulson, Stark, andJacobs 1977). Thus, every majormember of the class of hallucinogenicdrugs, agents which can cause an al-tered state of consciousness thatshares several common propertieswith dreams and with acute schizo-phrenia as outlined above, is unique-ly capable of exerting a pronouncedinhibitory effect upon the soma ofserotonin-containing neurons of thedorsal raphe nucleus. Other psycho-active drugs, such as the opiates, thebelladonna alkaloids (atropine), andtetrahydrocannabinol (THC), do notexert this primary physiological ac-tion, and produce altered states ofconsciousness which are clearly dis-tinguishable from those produced byhallucinogenic drugs (Jacobs 1978;Jacobs and Trulson 1979a).

Closely allied to the serotoninhypothesis of schizophrenia was theREM phasic event intrusion hy-pothesis (Dement et al. 1969). Thishypothesis held that a defectiveserotonin gating mechanism allowedsome phasic events of REM sleep tointrude into the waking state. It wasbased on the observation thatpharmacological or ablative inter-ference with serotonergic neurotrans-mission enabled the emergence ofpontine-geniculate-occipital (PGO)waves, monophasic slow potentialswhich are normally confined to REM

periods, into the NREM and wakingstates. The occurrence of these wavesseemed to coincide with halludna-tory-like behaviors in animals. It wasproposed that PGO waves were the"minimal neural substrate" (Dementet al. 1969, p. 792) of dream images,and that the intrusion of PGO wavesinto the waking state might give riseto the hallucinations of schizo-phrenia.

Further research demonstrated,however, that the eye movements ofREM sleep occur just before PGOwaves in the lateral geniculate body(Sakai and Cespuglio 1976). There-fore, the notion that eye movementsoccur in response to hallucinated vis-ual images caused by the intrusion ofphasic PGO waves must be rejected(Jouvet 1979). Furthermore, REMsleep occurs without interruptioneven after complete destruction of theascending PGO system (Laurent etal. 1977; Jouvet 1979). Thus PGOwaves are not the "minimal neuralsubstrate" of dream images.

Just as it was theorized that PGOwaves could explain the visual hal-lucinations of schizophrenia, so theywere invoked to explain the LSDstate. Since PGO waves were knownto be under serotonergic control, andsince LSD was known to inhibit thedischarge of serotonin-containingneurons, it was reasoned that LSDmight produce waking hallucinationsby introducing PGO waves into thewaking state (Stern, Morgane, andBronzino 1972). Experiments showedthat LSD in fact confined PGOwaves to REM periods (Henriksen,Jacobs, and Dement 1972; Brooks1975; Ruch-Monachon, Jalfre, andHaefely 1976). Thus PGO waves arenot the neural substrates of drug-in-duced hallucinations. Jouvet (1979)has concluded that PGO generatorsare responsible for the motoric pro-gramming of oneiric behavior.

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Serotonin or Dopamlne?

While enthusiam for the intrusionhypothesis had given new impetus tothe serotonin hypothesis of schizo-phrenia, its demise helped throw thelatter into disfavor (Mendelson,Gillin, and Wyatt 1977). At thesame time, the dopamine hypothesisgained ascendancy. This hypothesisis based upon two major find-ings: (1) Pharmacological agents thatdecrease dopaminergic activity haveantipsychotic properties, and (2)amphetamine increases dopaminergicactivity, and is considered by someinvestigators to produce a state thatis virtually indistinguishable fromparanoid schizophrenia (Meltzer andStahl 1976). The dopamine hy-pothesis may be in jeopardy (Alpertand Friedhoff 1980). Amphetaminesmay enhance the therapeutic effect ofphenothiazines (Fukuda and Mitsuda1979) and reduce psychotic symp-toms (Van Kammen et al. 1982) inschizophrenia. A review of the litera-ture on the use of MAOIs (whichtheoretically increase dopaminergicactivity) in schizophrenia showedthat these drugs either ameliorate orhave no effect upon the core psycho-pathological symptoms of schizo-phrenia (Brenner and Shopsin 1980).When L-dopa was added to pheno-thiazine regimen in the treatment ofseveral independent groups of schizo-phrenics, additional clinical improve-ment was observed (Fleming, Makar,and Hunter 1970; Inanaga et al.1975; Meltzer and Stahl 1976). Alpertand Friedhoff (1980) suggested thatthe timing of the onset of ampheta-mine psychosis coincides more close-ly with dopamine depletion than in-creased availability. All of the aboveresults would make a good case fordopaminergic hypoactivity, ratherthan hyperactivity, as being of etio-logical significance in schizophrenia.

While it is likely that dopamineplays some role in the pathogenesisof schizophrenia, it is apparent thatthere are a number of problems withthe dopamine hypothesis. Its ascen-dancy has gone hand in hand withthe ascendancy of the amphetaminemodel of psychosis. In regard to thelatter, Claridge (1978) has argued re-cently that the LSD state is a bettermodel psychosis than the ampheta-mine model. Recent work with ani-mal models of psychosis may clarifythis issue. In a series of experiments,Trulson, Jacobs, and colleagues de-veloped a reliable model for assessingbehavioral responses to a number ofpsychoactive drugs. They observedthe full behavioral repertoire of catsin response to various drugs andnoted in particular that limb flicksand abortive grooming were pro-duced consistently by LSD, psilocin,psilocybin, DMT, DOM, and mesca-line (i.e., all major hallucinogenicdrugs) and by parachlorophenylala-nine (PCPA), an inhibitor ofserotonin synthesis (Trulson andJacobs 1976; Jacobs, Trulson, andStern 1976, 1977; Jacobs et al. 1977).These behaviors were not seen fol-lowing the administration of a vari-ety of other psychoactive drugs, in-cluding amphetamine (Jacobs andTrulson 1979b). In another experi-ment, the investigators administered5-methoxy-DMT, a short-acting hal-lucinogen, and simultaneously meas-ured both the discharge rate of dor-sal raphe neurons (using subcorticalmicro-electrodes) as well as the num-ber of instances of abortive groomingand limb flicks (Trulson and Jacobs1979b). Both measures showed veryclear dose-response relationships. De-creases in unit activity in the dorsalraphe were correlated with increasedbehavioral responses. This was citedas strong evidence in favor of theserotonin hypothesis of hallucino-

genic drug action. The investigatorsalso related their experiment to anearlier one in which dorsal raphe unitactivity was recorded in freely mov-ing cats (Trulson and Jacobs 1979d).That study demonstrated a dramaticdecrease in the rate of dorsal rapheunit discharge as the animal wentfrom waking to NREM sleep to REMsleep. Jacobs and Trulson (1979d)concluded:

The oft-noted phenomenologicalsimilarity of dreams (which occurmost vividly in REM sleep) anddrug-induced hallucinations mightbe mediated, in part, by a commonneurochemical event—the inactiva-tion of central serotonergic neuro-transmission. [p. 401)

The Trulson and Jacobs model wasbased on their experiments whichshowed that only hallucinogenicdrugs produced "hallucinatory-like"behaviors in cats (including limbflicks and abortive grooming), andthat all drugs which produced thesebehaviors were known to depressserotonergic neurotransmission(Jacobs 1978). This model was chal-lenged by a report that long-termamphetamine administration in thecat led to a number of hallucinatorybehaviors, including limb flicks andabortive grooming (Ellinwood andKilbey 1977). This report encouragedTrulson and Jacobs (1979c) to re-examine the effects of amphetamineadministration upon behavior andserotonin metabolism in the cat.They found that short-term adminis-tration of amphetamine did not elicitthe behaviors in question, and pro-duced a small decrease in brain sero-tonin without any decrease in 5-hy-droxyindoleacetic acid (5-HIAA), theprimary metabolite of serotonin.However, long-term amphetamineadministration on a dosage scheduleequivalent (on a milligram ofdrug/kilogram of body weight basis)

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to that which typically producesamphetamine psychosis in humansproduced the "hallucinatory" be-haviors and resulted in large de-creases in serotonin and 5-HIAA inall brain regions examined. The ap-pearance of the behaviors and theserotonin decrements followed atime-course that parallels the typicalappearance of psychotic symptoms inhuman amphetamine psychosis.Thus, the serotonin hypothesis canaccount for the onset of "hallucina-tory" behaviors in both the ampheta-mine model and the hallucinogenicdrug model of psychosis in the cat.An identical time course for theappearance of hallucinatory be-haviors following chronic ampheta-mine administration has been seen inrats (Nielsen, Lee, and Ellison 1980)and in monkeys (Ellison, Nielsen,and Lyon 1981). Since the timecourse of these behaviors is virtuallyidentical to that which is seen inhumans, there is a strong possibilitythat changes in serotonergic neuro-transmission may occur in the chemi-cal model of psychosis in man.

The serotonergic model of dreamsand hallucinogenesis presented abovehas a number of difficulties. In cats,the behavioral effects of LSD outlastthe depression of dorsal raphe unitactivity by several hours (Trulsonand Jacobs 1979a). Readministrationof LSD 24 hours after the initial doseproduces marked depression of rapheactivity, but little behavioral effect.Dissociations between raphe unitdepression and "hallucinatory" be-haviors have also been seen withother hallucinogens (Trulson, Heym,and Jacobs 1981). Lisuride, anergoline derivative, exerts a rapid, di-rect inhibitory effect on dorsal rapheneurons (Rogawski and Aghajanian1979), produces limb flicks and abor-tive grooming in cats (White, Holo-hean, and Appel 1980; Marini et al.

1981), but is not hallucinogenic inman. Mescaline, unlike other hal-lucinogens which produce a direct ef-fect, produces only an indirect sup-pression of dorsal raphe unit activity(Haigler and Aghajanian 1973). Asfor the dramatic depression of rapheunits that occurs during REM sleep, arecent experiment involving pontine-lesioned cats that display REM sleepwithout atonia suggests that the dis-charge rate of raphe units may reflectchanges in motoric activity ratherthan changes in state of conscious-ness (Trulson, Jacobs, and Morrison1981). The lesioned cats showed onlya small decrease in raphe unit activ-ity in passing from waking to NREMsleep to REM sleep compared withnonlesioned controls.

These findings question the signifi-cance of the discovery that dorsalraphe neurons behave similarly inREM sleep and in hallucinogenicdrug states. Nevertheless, the pre-ponderant evidence currently favorsa role for a common mechanism, de-pressed serotonergic neurotrans-mission, in these states (Jacobs andTrulson 1981; White and Appel1982).

Mandell (1980) tested a variety ofpsychoactive agents and found thatonly hallucinogens inhibit raphe cellfiring without a compensatory in-crease in serotonin synthesis. WhenLSD is given in conjunction withPCPA, an inhibitor of serotonin syn-thesis, the effects are synergistic(Trulson and Jacobs 1976). In man,depletion of serotonin by reserpineenhances the effects of hallucinogens(Isbell and Logan 1957; Freedman1963; Resnick, Krus, and Raskin1965). MAOIs (which theoreticallyincrease serotonergic neurotrans-mission) attenuate the effects of hal-lucinogens (Sai-Halasz 1963; Resnick,Krus, and Raskin 1964) and suppressREM sleep. LSD hastens the onset

and prolongs the duration of REMperiods (Muzio, Roffwarg, and Kauf-man 1966).

Other data that suggest convergentmechanisms have implications forschizophrenia. LSD and PCPA pro-duce identical "hallucinatory" be-haviors in cats (Dement et al. 1969;Trulson and Jacobs 1976). PCPA-treated cats do not exhibit a REM re-bound after experimental REM sleepdeprivation. Human sleep studieshave shown consistently that acuteschizophrenics do not have a REMrebound after experimental REMsleep deprivation (Neale and Olt-manns 1980). In man, PCPAadministration suppresses REM sleep,but is not followed by a REM re-bound upon drug termination(Mendelson, Gillin, and Wyatt 1977).The REM sleep abnormality and hal-lucinatory behaviors produced byPCPA in cats are reversed byadministration of 5-hydroxy-tryptophan, a serotonin precursor, orby chlorpromazine, a drug used inthe treatment of schizophrenia (Zar-cone 1979). There is a substantialbody of electrophysiological (Milleret al. 1975; Dray et al. 1976; Bunneyand Aghajanian 1976), anatomical(Miller et al. 1975; Pradhan and Bose1978), behavioral (Costall and Nay-lor 1974; Costall et al. 1975; Giam-balvo and Snodgrass 1978; Wald-meier and Delini-Srula 1979; Carterand Pycock 1979), and biochemical(Kuczenski 1979) evidence in supportof a putative role for serotonin in thedirect inhibition of dopaminergicneurotransmission in the substantianigra, neostriatum, and nucleus ac-cumbens. A depression ofserotonergic neurotransmission,which, as detailed above, is preciselywhat takes place during hallucino-genic drug and REM sleep states,would result in a loss of this in-hibitory influence. Such a mechanism

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could be invoked to explain the puta-tive dopaminergic hyperactivity with-in these structures which forms thebasis of the dopamine hypothesis ofschizophrenia.

It is well established that an under-standing of interactions amongneurotransmitters is a crucial steptoward understanding themechanisms responsible for regu-lating REM sleep (Pujol, Keane, andJouvet 1978; Morgane 1981). Surelya knowledge of such interactions willimprove our understanding of hal-lucinogenic drug states and schizo-phrenia as well. The recent findingthat LSD, mescaline, psilocin, andDMT, but not lisuride ormethysergide (a serotonin an-tagonist), are uniquely capable offacilitating the excitatory effects ofserotonin and norepinephrine uponfacial motoneurons (Aghajanian1981) is intriguing. The currentlypopular activation-synthesis model ofdreaming holds that dreams occurwhen certain pontine reticular cells(FTG cells) become excitable throughthe loss of serotonergic and nor-adrenergic inhibitory influences(Hobson and McCarley 1977).

It is probable that dorsal rapheunit activity is mediated by tonicnoradrenergic input and by self-regulatory serotonin autoreceptors(Aghajanian 1981). An agent whichbehaves as a specific autoreceptor an-tagonist might prevent the reductionof raphe unit firing which normallytakes place during REM sleep andhallucinogenic drug states. Be-havioral studies could clarify whetherreduction in dorsal raphe activityplays an essential role in the psy-chological manifestations of thesestates. The basic analogy elaboratedin this article dictates that a pharma-cologic agent which can: (1) an-tagonize a biological mechanismwhich is common to hallucinogenic

drug states and REM sleep; (2) at-tenuate the psychological effects ofhallucinogens and suppress REMsleep (or reduce the primary processcontent of dreams) may be of poten-tial benefit in the treatment of acuteor incipient schizophrenia. It ishoped that continued research intothe mechanisms of dreams and hal-lucinogenic drug states will augmentresearch into the mechanisms ofschizophrenia, and vice-versa. Byunderstanding the similarities anddifferences between these three states,it may become possible finally tovalidate the comparisons made be-tween them throughout the recordedhistory of philosophy and medicine.

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The Author

Lawrence G. Fischman, M.D., is aresident in psychiatry at the PayneWhitney Clinic, The New York Hos-pital-Cornell Medical Center, NewYork, NY.

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