Journal of Psychoactive Drugs

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Psychoactive Drug Research in the Soviet Scientific Tradition Leonid I. Spivak To cite this article: Leonid I. Spivak (1991) Psychoactive Drug Research in the Soviet Scientific Tradition, Journal of Psychoactive Drugs, 23:3, 271-281, DOI: 10.1080/02791072.1991.10471588 To link to this article: https://doi.org/10.1080/02791072.1991.10471588

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Psychoactive Drug Research in the Soviet Scientific Traditiont Leonid I. Spivak* Abstract - During the past 200 years, Soviet scientists have extensively investigated and evaluated the effects of psychoactive drugs in humans. An examination of the resultant literature provides insight into the four distinct periods that comprise this era of research. Keywords - altered states of consciousness, LSD, psychiatry, psychoactive drugs, psychopharmacology, USSR

Soviet science has a rich tradition of research in the field of psychoactive drugs that is abundantly reflected in the literature. The present author, a clinical psychiatrist, has used psychopharmacological drugs in his practice and considered their effects in discussions with leading Soviet colleagues, including pharmacologists and psychopharmacologists. The present author has described his approach to the objective evaluation of psychoactive drug effects in Psychotomimetics (Milshtein & Spivak 1971), while the results of that research over the past two decades have been summarized in Side Effects of Psychopharmacotherapy (Spivak, Raiski & Vilenski 1988). Admittedly, the difficulty in objectively evaluating psychoactive drug effects in humans remains as problematic as at the start of the research. One 's first impression from the available data is a certain degree of similarity in the Soviet and American scientific research traditions of approaching the problem of objective evaluation as well as the conclusions that have been drawn. This can be seen not only in the trend of research but in its limitations as well: the 1966 American ban that imposed limits on the psychodysleptic treatment of healthy people and the 1967 Soviet ban on the administration of lysergic acid diethylamide (LSD) to human subjects (Babayan & Utkin 1982); animal experiments required special permission of the Permanent Committee

for Drug Control for every experimental series. The importance of permanent social control of such research is beyond any doubt. Its actual form, however, led to inhibiting the studies rather than channeling them in another dircction. The question of the optimal form of such bans appears justified but is beyond the scope of the present article. Another impression is the difference in the studies of psychoactive drugs in the Union of Soviet Socialist Republics (USSR) and the United States. It is important to bare in mind that the Soviet scientific tradition is marked by maximal amalgamation of physiology and medicine on the grounds of the theory of nervism . The founders of the concept, Sechenov and Pavlov, regarded nervism as "... a physiological trend, aimed at extending the influence of the nervous system over the maximal possible functions of the organism" (pavlov 1940). Nervism prevailed in the Soviet tradition from the 19308 through the 1970s, but even now students start from this basis, especially in their theoretical generalizations. It would be reasonable to assume that with each difference between the Soviet and American approaches to psychoactive drug research one is seeing two branches of the same tradition. A comparison of the differences enables one to shed light on the general situation as well as on the sprouts of new directions. The present article is a beginning to such a dialogue. In the following discussion, two basic aspects will be considered: the general progress in psychoactive drug research in the past 100 years and trends in the basic perspective. The latter comprises the traditional approach of the modeling of psychotic disturbances through psychoactive drugs and the nontraditional study of altered states of consciousness (ASC) by means of psychoactive drugs.

tTranslated from Russian by the author. (Editor 's note , Recent events in the Soviet Union have compounded already difficult communication problems. Every reasonable editorial effort has been made to maintain the author's intent and the integrity of the text; however, some textual information - particularly in the references - was not provided and could not be determined under the present circumstances.) -Human Brain Institute, Academy of Sciences of the USSR, Nevski pro 22-19, Leningrad 191 186, USSR. JOUTNl/ ofPsychoactive Drugs

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Exam ination of the Soviet scientific literature on the effects of psychoactive drugs enables one to distinguish four distinct periods since the beginning of the nineteenth century. In the first period, which lasted from the beginning of the nineteenth century until the 1920s , psychoactive drugs were regarded traditionally in the world of science for medical and diagnostic purposes. However , this was also the time of the development of the paradigm of future thinking; some features extend into the present. In the second period, the 1930s and 1940s, there was a decrease in the total volume of research, while the theoretical potential increased. In the third period, which was during World War II (1941-1945), psychoactive drugs were used widely as remedies in extreme conditions . Although hampered by wartime conditions, important investigations about the interaction of the drug and the organi sm wer e carried out. Finally, in the fourth period , psychoactive drugs were used more broadly as part of psychopharmacological treatment, and some theories concerning their modes of action were formed , some of which exceeded the limits of traditional medi cal research.

drug s affect con sciousness. In particular, he proposed to distinguish hallucinations in relation to one's state of consciousness: " . .. there exi st two type s of halIucinations with a certain degree of clouded consciousness and without its disturbance." In the first case, the hallu cination s arise (in the present author 's opinion) from the involvement of "s ubcortical sensory centers ," and in the second, only the brain cortex is involved. The investigation of the influence of psychoactive drugs on consc io us nes s attract ed the attention of the prominent Ru ssian psychiatrist Bckhterev (19 28, 1896, 1888) who dwelt parti cularly on "in complete" con sciousness (i.c., the state of consciousness that occurs in the co urse of action of psychoactive dru gs and in som e psychical disturbances). In his investigation of consciousness, Bekhterev stressed its profound individuality and proposed to differentiate the degrees of con sciousne ss by their content: from the primitive to the more complicated (i.c., consc iousness of personality or of tim e) to the high est (i.e. , analy sis of proper psychic processes). Dur ing this time, psychiatrists also analyzed the clin ical effects of such psychoactive substances as ergot, arscnic. Iead, mercury, and pho sphorous (Kolotinski i 1902; Popov 1882; Danillo 1880). A number of vo luminous monographic work s dealt with the influence of alcohol on the human psyche (Nil sen 1906; Kolpakov 1886). Also worth mentioning is the research concerned with the indu ction of halIucinations by smalI doses of soporifi cs (Osipov 1923) and the restoration of previous halIu cinato ry phenomena by mean s of psychoacti ve drug s (Triumfo v 1923 ; Zaitzev & Ivanov 1907 ). Thu s, during the first period in the study of psychoactive drug s, their practical value as diagnostic and medical substances was demonstrated, and con cepts were formu lated about clinical effect being dependent on drug dosage. The theoretical value of the research rested on the discovery of the possibility of their effect on the state of conscio usness.

THE FIRST PERIOD In the first Soviet manuals of psychiatry (Balinsk i 1858; Pu shkarev 1848; Malinovski 1847; Butkovski 1834), con siderable attention was paid to the clini cal effects of psychoactive drugs that were then in curr ent use: opium, belIadonna, some ethers, and volatile alkali. In 1863 , Dukov wrote a monograph about the influence of opium on the human psyche. His review of the case histories of Russian psychiatric institution s substantiated that psychoa ctive drug s were prescribed more frequently than drugs that did not affect the central nervous system (eNS). During the nineteenth century, opium and extract of Cannabis indica were often used in psychiatry as rem e.die s in emotiona l di sturbances and in acute and chronic psycho ses, and as diagnostic drugs for the provocation of delirium and halIu cinations. Thu s, Kandinski (1890) appl ied this diagnostic method in his work that appeared in the wid ely known book About Pseudo hallucinations. For example, in the description of a subjec t who had had a psychosis, but at the time of examination exp eri enc ed neither delirium nor halIucinations, Kandinski reported that " .. . treating him from time to time , before going to bed or at daytime with opium or extract of Cannabis indica, I induced in him very vivid so-calIed hypnagogic halIucinations and listened after that to a detailed account of his observations done in this state. By way of such experim ents we succeeded in rather exhaustive research of those hallucinatory and pscudohallucinatory phenomena, which arc experienced by many normals in the state of passing from being awake to sleep." Kandinski was the first to mention that psychoa ctive Journal of Psychoactive Drugs

THE SECOND PERIOD T he decrease in the total volume of studie s in the second period coincided with the general limitations set on the development of psychological testing and diagno stics. Nevertheless, at thi s time profound clinical studies of the effects of psy choactive dru gs were accomplished, including those by Sumbaev (1937,1932), Ronchevski ( 194 1, 1940, 19 39, 1938 , 1937 ), and Aleksandrovski (1936, 1934). Sumbaev examined the effects of psychoactive drugs on various psychopathological phenomena and documented that they not only have anti symptomatic effects but that the substance and its dose - being correctly chosen - can also abrogate the manifestation of psychosis . 272

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Atropine, scopolamine, adrenaline, and veronal efficiently diminished or totally abolished the oneiroid phenomena (resembling a dream) for several days. Contrary to this, eserine and pilocarpine intensified the psychopathological symptoms. Aleksandrovski and Ronchevski investigated the effects of psychoactive drugs not only in patients but in normals as well. Aleksandrovski's studies detailed the effects of mescaline: the onset of the disturbance of consciousness, followed by disturbances in visual analysis. Special attention was paid to the "memory track" left by mescaline in the nervous system. Experimenting on himself, Aleksandrovski observed recidivistic manifestations of mescaline effects after one to two hours, after one to two years, and even after 20 years (Aleksandrovski 1964), when "as a result of infection, followed by asthenia, at falling asleep all experience of mescaline intoxication was restored nearly completely." Formation of a memory track is universal for the effect of a psychoactive drug (Aleksandrovski 1964, 1958, 1936, 1934). Ronchevski investigated one state of consciousness under the action of mescaline and tried to research the sensorial nature of visual hallucinations. For this purpose, along with clinical examination, an investigation of visual imagery in conditions of adaptation to darkness was carried out, which enabled the author to conclude that conscio usness is altereddue to the action of mescaline: the higher intellectual processes are inhibited, while the activity producing and reproducing visual imagery is en hanced. Ronchevski observed (1941) the following after mescaline injection:

the effects of other psychoactive drugs, including opium, morphine, and hashish (Strelyukhin 1942; Travinskaya 1942). Gorovoi-Shaltan (1942) revealed regular alterations of the neurological state following the injection of morphine and, in particular, the symptoms of disinhibition of subcortical formations at the onset of withdrawal or after the effects wore off. It should be mentioned that the effects on higher nervous system activity by the psychoactive drug bulbocapnine, which provokes catatonic symptoms, were thoroughly studied at that time in Pavlov's laboratories (Deryabin 1939; Kleschev 1938). The famous experiments on the effects of bromide and caffeine on animals and, to a lesser degree, on humans in a neurotic state were also being conducted (Pavlov 1940; Poznanski 1936). In addition, experiments with mescaline injection into animals were completed (Aleksandrovsk i, Babskii & Kryajev 1937). Thus, in the second period, the effects of psychoactive substances were studied mainly in clinical conditions, al though some studies were being carried out with animals. Selectivity of their effects was demonstrated: mescaline on the visual analyzer and higher mental function s, bulbocapnine on the motor analyzer, and both with memory track evaluations. In the field of theory, an idea was tentatively advanced concerning the possibility of the qualitative restrictions of con sciousness, which was termed "structural damage." Of interest were conclusions about the integration of mescaline-induced alterations into the clinical picture of psychotic disorders.

THE THIRD PERIOD . , , the alterations increased slowly, and the first of them was an overall shift in self-feeling and in relation to the surroundings, which I should defme as a "tum of the whole psychological attitude from real objects to proper experiences ," I was reminded of the slate of the feverish patient: The consciousness is being overwhelmed by subjective images, and the threads, which actively associate us with the surrounding world are kind of tom off. The inverse attitude of consciousness, aimed at inner experiences, proved to be connected with sensory illusions, arising somewhat later.. .. Seemingly, this slightest degree of alteration of consciousness corresponds to the initial stage of confu sion . Contrary to the confusion, however, perceptions did not fade, but became bright and rich.

The outbreak of World War II was not favorable for the development of science or for the topic under consideration in particular. In this respect one could mention the destiny of Ronchevski, who was killed in the trenches at the very beginning of the war. His monographs appeared in a limited number of copies, almost immediately became a bibliographic rarity, and hence he is not well known by specialists. The present author hopes that in future anthologies on psychoactive drugs his works will occupy their deserved place. In the verbal tradition, the importance of his research is beyond any doubt. The present author remembers how Ronchevski 's colleagues, professors Osipov and Gorovoi-Shaltan - as well as other Soviet psychiatrists, Ivanov-Smolenski (1952), Gilyarovski (1949), and Popov (1941) - used to begin with an account of Ronchevski 's results in their interpretations of the mechanisms of consciousness and hallucinations. In the third period of investigation into the effects of psychoactive drugs, efforts to help the wounded, confused, and diseased in the extreme conditions of war was dominant. Previously studied psychoactive drugs were being

Ronchevski (1941) also reported that the elevation of mescaline dosage leads to "transformation of structural alteration of consciousness into a deeper derangement." Ronchevski (1941) wrote that "I feel justified to state that it is possible to experience . . . [being] completely projected into milieu hallucination, being in a state which does not exclude accounts about the experiences and their evaluation." The essence of the mescaline hallucinatory state is that sensory disturbances are its most typical component (Ronchevski 1940, 1939, 1938, 1937). At the same time, some studies were carried out on )OIUNJ{

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used for humanitarian purposes, particularly in the treatment of traumatic surdimutism (deaf-mutism), acute affective reactions, shock, neuroses, and other diseases of the nervous system (Ravkin 1949). Most characteristic of this period was an extreme sensitivity to neurotropic substances ofthosc who participated in battles. Formally, these substances (e.g., tetraethyllead, trinitrotoluene, hexogene) cannot be considered psychoactive drugs, but they quite unexpectedly revealed some psychoactive properties. Even a single application at a minimal dose caused pronounced reactions of mental activity. Special research revealed that it was due to unfa vorable changes in the functional state of the organism. Grave conditions developed when two effects coincided: the substance and closed-brain injury, when the substance affected overstrained people, or those suffering from psychogenic disturbances or other problems due to wartime stress. Clinical examinations (Ravkin 1949) revealed some particularities not observed before the war (e.g., pronounced vegetovascular disturbances and the development of organic lesions in the nervous system). It is no wonder that certain authors (e.g., Portnov 1956) proposed a new nosological category - acute tetraethyllead psychosis.

derivatives and continued with those of glycolic acid and other substances. Psychoactive drugs were frequently administered to normals (most often in self-experiments) but also to patients with psychopathologic symptoms. Animal experimentation also gained in importance. The first communications on the effects of psychodyslcptics on humans were published by Banschikov and Stolyarov (1964, 1959), Nadjarov, Morozova and Smulevich (1962), Rappoport and Lando (1962), Sncjncvski (1961), and Morozov (1957) . In a review article by Stolyarov (1964) titled "Drug Psychoses and Psychotomimetics," a considerable volume of clinical data was presented about the effects of mescaline, LSD, bufotenine, dimethyltryptamine, dicthyltryptamine, benactyzine, and ditran (1B-329) on healthy people. Stolyarov emphasized the diagnostic value of LSD for differentiation between endogenous psychoses and borderline states, and its therapeutic value in the treatment of neuroses and chronic alcoholism. His opinion was that psychoactive drugs have distinctive effects on both patients and controls (e.g., the reaction to mescaline is similar in both, whereas psilocybin produces different types of reactions). In addition, exhaustive data from the literature were presented concerning serotonin and adrenaline metabolism in mental disorders. Banschikov, Korolenko and Korolenko (1968) and Muchnik (1965) studied the human clinical effects of LSD and concluded that LSD-induced psychoses are reactions of an exogenous type. Delirium syndromes, characteristic of the latter, occur rarely under the influence of LSD, while the phenomena - bright visual hallucinations that arc very rich in colors - are generally assessed as predelirious and arc permanently recorded. As a rule, the occurrence of altered perception of time was the most characteristic effect of LSD . It should be noted that the authors met with great difficulties in their attempts to describe in clinical terms the psychological state of their subjects under the influence of LSD. They could only point out the "chaotic mental activity," the "strange and unusual perception of the flow of time," and the "alterations of basic communication patterns." This clinical picture of LSD provided unusual data for psychiatrists. Therefore, the conclusion that the metalanguage of modem psychiatry is insufficient for description of the action of LSD is justified. One of the characteristic features of the actions of psychoactive drugs that was revealed in early research is a very particular relation to time. Subjectively, it is expressed by adults in episodes of visual childhood pseudoreminiscences, as in versatile changes of time perception. Objectively, in the above-mentioned delayed effect of the substance, it was defined as a "primarily compensated" form of reaction . The term was introduced, with orientation to a great number of clinical observations, when the drug's action manifested itself after a period of

THE FOURTH PERIOD In the fourth period of research on psychoactive drugs, two subperiods can be considered separately. The first subperiod, which includes the 1950s-1970s, was marked by the synthesis of a great number of psychopharmacological agents in general and psychoactives in particular, with their broad adoption in medieal and diagnostic practice. The second subperiod, which covers the 1970s to the present, was marked by the appearance of review monographs and attempts to develop theories of modes of action of psychoactive drugs. It should be emphasized that the principal approach to the objective evaluation of psychoactive drugs in humans will to a considerable extent determine the conclusions to be drawn. Thus, while psychoactive drugs and psychodysleptics found their place in psychiatry and pharmacology courses during the first subperiod (Pidevich 1977; Portnov & Fcdotov 1971; Zakusov 1966; Salyamon 1961), they were practically neglected in the corresponding courses of the second subperiod (Morozov 1988; Komendantova & Zorina 1988; Lepakhin, Belousov & Moiseyev 1988; Kharkevich 1987; Snejnevski 1983)presumably because the theorists of mainstrcarn psychiatry were not interested in these drugs at that time. During the first subperiod, there was an increase in the volume and the nomenclature of the psychoactive drugs used for medication and for diagnosis, as well as the range of pathological states examined with their use. The process began with the application of lysergic acid JOUTnal of Psychoactive Drugs

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time, as an action of a new exogenous factor. The response reaction developed even when the effect of the latter was preceded by a period of absence of contact with the psychoactive drug (Banschikov, Korolenko & Korolenko 1968; Muchnik 1965; Spivak 1964). At this point in time , an understanding of the mech anisms of action of psychoactive drugs acquired more interest, and more researchers studied the effects of drugs in animals. TIley had already shaken off the extreme views that relevant information cannot be obtained from animal experiments or, to the contrary, that data obtained from animal experiments are relevant for humans without corrections. As a result of a series of research studies carried out under the guidance of the psychiatrist Goldenberg from 1941 through 1961, it was realized that subtle changes in the psyche can be traced in animals: transformations of complexes of fixed movements; catatonic and asthenic syndromes; syndromes of disturbed consciousness (delirium , confusion, twilight); and particularities of infonnation processing and communication. A monograph edited by Goldenberg (1957), Reproduction ofSome Symptoms ofAtropine "Psychosis" in Animals, asserted that a scientist reproducing so-called model psychoses in animal s has to master clinical methods of investigation. In the first subperiod, the newly developed method of narcodynamic investigation was applied. The method was based on the ability of psychoactive drugs at certain doses and at certain periods of action to simplify some psychopathologic phenomena. The use of this method con tributed to a more accurate evaluation of the psychopathologic picture and facilitated diagnosis of various mental disorders. Of a great number of substances that were examined, hexenalum and barbamylum proved to be the most effective. In relation to the intensity and stage of the basic disorder, various rapidity of effect development, peculiarities of disturbances of consciousness and thought, and disturbances of affectivity were recorded (Khaletzki 1964, 1963). An important document was published in 1964 as a special issue of the Journal of the National Chemical Society (Volume 9, Number 4), which summarized some of the results of psychoactive drug research in the first subperiod. The purpose of the articles was to discuss the possibility of a general paradigm that could coordinate biochemical, physiological, chemical, psychiatric, and psychological studies. The main ideas were the assertion of the chemical origin of psychoses as being the most prospective for understanding their mechanisms, the essential role of cateeholamines in mental activity, and the ability of psychotomimetics to substitute for mediators and alter the corresponding metabolism as the important peculiarity of psychotomimetic action. This is why three groups of psychotomimetics (i.e., serotonin-, adrenaline-, and acetylcholine-related) were considered. Yarovenko (1964) stressed that " ... in animals, the effect of psyJOUTN:l1

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chotomimetic substances depends not only on their chemical structure, but as well on the individual differences and on the state of the organism at the period of action (i.e., on the whole earlier life) and on the dosage of the substance." In the second subperiod, the volume and quality of the earlier investigations allowed the publication of summational works. Thus, in the book Psychotomimetics, Milshtein & Spivak (1971) based their conclusions on more than 800 well-founded experimental studies of Soviet and foreign researchers. Two groups of psychotomimetics were examined in the book: the derivatives of glycolic acid and lysergic acid. The research on the mechanisms of psychotomimetic activity of the glycolic acid derivatives revealed the existence of a direct connection between psychotomimetic and central M -cholinergic properties. The cholinolytic mechanism proved to be essential in the development of psychotomimetic effects. Cholinolytics require a considerable increase of acetylcholine content, which is also important for determining the mechanisms of dysleptic effects of cholinolytic psychotomimetics. The interpretations of the effect of these substances on the metabolism of pyrocatechinamines are to som e degree contradictory. Milshtein and Spivak analyzed the mechanism of action of LSD on the CNS and demonstrated that the effect was dose dependent, The effect can be inhibition of serotonin action on synaptic receptors or, to the contrary, its enhancement. Both can entail psychological disorders. Further research connected the interaction of LSD and serotonin directly at the receptor level. In sum , the psychotomimetic effect of glycolates is due to M-cholinoreceptor blockade in the CNS, while that of LSD is probably associated with catecholamine or acetylcholine metabolism or secondary changes in serotonin metabolism . As far as the particularities of the clinical effects of psychotomimetics are concerned, the principal differences of these two groups should be stressed. Cholinolytics of central effect primarily induce disorders of consciousness that can be maintained with repeated injections of the drug. Clinical signs in both controls and in mental patients are similar. The effect of lysergic acid derivatives clearly indicates a change in the entire psyche, which affects personal experiences. They produce different reactions in patients and controls, and have a closer relation to personality types. Changes in perception of time are distinctive for the effects of cholinytics (but to a lesser degree than that of LSD). This quality comes to light even at small doses. Detailed clinical research of the effect of atropine and glycolates was performed by Bazhin and colleagues (Bazhin 1984, 1973, 1967; Bazhin & Meyerson 1972; Bazhin & Sprintz 1968) who mainly concentrated on their therapeutic value. Bazhin minutely examined the effect 275

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of high doses of benactyzine and demonstrated the efficiency of this drug in therapy-resistant forms of schizophrenia. The value of animal experiments conducted during this subperiod should be emphasized. It was found that psychoactive drugs in doses that cause pronounced disorders in humans resulted (when adjusted to body weight) in appreciable disturbances in animal behavior as well as in shifts in electrophysiological and biochemical data. These conclusions were drawn from the results of studies of the behavior and conditioned-reflex activity that was influenced by the effects of LSD and glycolates in mice, rats, dogs, and monkeys (Mesh man 1966; Apter & Vyunitzkaya 1965; Arbuzov etal. 1965; Dcnisenko 1965; Ivanova et al. 1964; Vavilova, Klyavina & Obraztsova 1%3; Ivanova, Laricheva & Milshtein 1962; Krylov & Snegirev 1962; Lagutina, Laricheva & Milshtein 1962). Further investigation of the objective evaluation of psychoactive drug effects was carried out in the direction of the mechanisms and peculiarities of action of particular substances; the relevant literature includes that of Khristolyubova (1977), Matveyev (1976), Matveyev and Chudina (1973), and Chudina (1972). The authors studied the effect of LSD on the higher nervous activity of animals and estimated pathomorphological alterations in the brain. The psychoactive effect proved to be due to the influence of LSD on the brain structures, particularly the phylogenetically younger regions of the cortex, thalamus, subthalamus, and corpus striatum. Of particular importance is that morphological alterations in neural parenchyma after chronic administration of LSD were not completely reversible. No less important was the conclusion about the time of appearance of compensatory restorative reactions, which occurred at the end of the second week after discontinuation of LSD injections. This effect occurred only after the usc of LSD and after its combination with haloperidol. Research into the mechanisms of psychoactive effects in animals was conducted by Anokhina (1975). Electrodes were implanted in the formatio reticularis of the mesencephalon, some thalamic and hypothalamic nuclei, and the corpus amygdaloideum. Specific activation of catecholam ine systems in certain parts of the brain and the effect on trunk and limbic structures of the CNS were shown to be the essence of biochemical mechanisms of psychotomimetic action. Separate cellular formations with high chemical sensitivity. to LSD, benactyzin, and marijuana were found in the formatio reticularis of the mid brain. These formations reacted in the same manner to different psychotomimetics but failed to react to substances devoid of psychotom imetic properties. Anokhina (1975, 1970) argued that the psychotomimetic-induced pathological state was based on a pacemaker mechanism (i.e., psychotomimetics and their Journal ofPsychoact ive Drugs

derivatives primarily affect those nervous structures that arc specifically sensitive to them). Alteration of the function of these structures triggers off the subsequent disturbances in neurochemical and neurophysiological functions of the CNS . On the basis of these data, Anokhina concluded that common principles might underlie the mechanisms of action of psychotomimetics that arc different in chemical structure. However, this conclusion found no confirmation in other works. In recent years, animal research concerned with pharmacokinetics and mechanisms of action of different psychoactive substances have been in progress. The studies that seem to provide the best perspective arc tho se on the pharmacokinetics of neurotropic drugs in th e brain (Fateyev, Solyaev & Titov 1985 ; Fateyev, Titov & Solyacv 1982), the effects of glycolates on stress in animals (Zakirov, Shaislamov & Teshabaev 1986), can nabinol-induced peculiarities of behavior (Machula & Barkov 1988), and peculiarities of the effect of M -choline blockers (Sprintz, Vinogradov & Komshinskaya 1988). At the end of the second subperiod a new di rection of research was revealed that was connected with the geographical position of the Soviet Union. A number of traditional medical cultures employing sophisticated psychoactive drugs (and mixtures) exist in its vast Asian territories. What is most important for the purposes of the present review is the Buryat version of traditional Tibetan medicine that was adopted in cuILural centers on contemporary medicine in the Soviet Union. At the beginning of the twentieth century, s uc h books as the Gen eral Handbook in the Medical Scien ces ofTibet: "Zhud-shih" (Badmaev 1903) and the Manual of Tibetan Medi cine (Pozdneyev 1908) were published in the Ru ssian language, which immediately attracted the attention of specialists in medicine, philosophy, and ethnography. P.A. Badmacv, a well-known advocate of Tibetan medicine, developed an intensive educational program in St. Petersburg. In the 1930s, his successor N. Badmaev created the Leningrad Initiative Group, with the purpose of "constructing the new medical science on the basis of synthesis of Oriental and European medicine" (Kochetov 1973). However, this activity was soon prohibited, and was not revived until the 1970s. A modern Soviet specialist in Tibetan medicine, Bazaron (1987) stated that "starting from sophisticated conceptions concerning the disease and mechanisms of its emergence, Tibetan medicine has over centuries elaborated a rather peculiar approach to treatment and prophylaxis of diseases. Its therapeutic notions include life regimen, dietetics, physical methods, [and] multicomponent medicinal substances," as well as nature, which " . .. by its richness and diversity represents a special world of drugs." This special world includes such psychoactive drugs as Cannabis indica, henbane, poppy, and metal salts. When the present author personally observed the med276

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ical activities of lamas of Agrinsky dacan (a Buddhist religious center in Siberia), he was particularly impressed by the individualized approach of the lamas to every patient. Later he was informed that such an approach is due to the essence of treatment. Tibetan medicine presumes different effects of the same substance - psychoactive among them - in different patients. These effects are dependent on their constitution, age, sex, eating schedules, and functional state at the moment of ingestion of the drug, as well as the time of day. As a rule, multicomponent mixtures are used (usually more than four components) in different proportions. Inasmuch as many patients find shelter in the dacan until treatment is accomplished, the lamas can investigate them in sufficient detail. Psychoactive drugs are a part of many mixtures and are recommended in the treatment of psychogenic disorders and diseases of the stomach or intestines. There is another tradition based on the Far Eastern traditional medical cultures (e .g., Chinese, Korean) . Modem representatives of these cultures work with psychoactive drugs of a new group called adaptogens, the most effective of which are Schizandra chinensis, radix Ginseng, and Aralia manchurica. Research has revealed that their adaptogenic effect is based on optimization of the energetic (and partially plastic) processes basic for functional states of the organism (Brekhman 1964). Adaptogens led to considerable insights into the treatment of the so-called third states, intermediate between health and disease, which have attracted more and more consideration in recent years. Medical recommendations are based on the traditional values of the Siberian and Far Eastern medical cultures and the fact that theoretical results have received documented practical realization (Massachetov 1985; Brekhman 1980, 1977; Saraev 1974; Unsigned 1974). In these works, another important aspect of the application of psychoactive drugs was developed: prophylaxis. In addition to the historical development of Russian research into psychoactive drugs, East Slavonic medicine should also be mentioned. Specialists in the history of medicine have recently shown that in old Russian medicine, psychoactive drugs were an integral part of therapy. In particular, henbane and ledum were described and used as early as the eleventh century, opium from the thirteenth century, Cannabis indica from the fifteenth century, and coca-related preparations from the sixteenth century (Bogoyavlenski 1960, 1956). The scientific investigation of this era was done in cooperation with historians and ethnographers. Thus, the most recent period of study of psychoactive drugs is marked by a striking increase in their number through the development of new substances with mainly psychodysleptic activity. They are broadly prescribed in cases of psychopathology and also for prophylaxis. Their JOIUNJI ofPsychoactive Drugs

mechanism of action was studied in detail, which made a signigicant contribution to the knowledge of the pathogenesis of mental disorders in general. Evaluating the achievements of this period, one can state that it has supported the important, although traditional, objective of medicine to affect the human psyche for needs of psychoprophylaxis and the treatment of mental disorders in an active and pathogenetically justified manner. SUMMARY AND DISCUSSION In summarizing the effects of psychoactive drugs, two main trends can be distinguished: the modeling of mental disturbances and the study of ASC. The former has been more thoroughly investigated both in the Soviet and the American traditions. The comparative value of both trends seems less important than the inner connection between the two traditions. There are two possible points of view. First, they can be considered to be absolutely disconnected. This view has its theoretical and practical justifications. It is the concept of depersonalization being independent from alterations of consciousness (Milshtein & Spivak 1971). Second, normals and mentally ill patients react differently to cholinolytics and LSD, so that the following question arises: Do model psychoses in mentally ill patients correspond to ASC in normals? Both trends can be regarded as two aspects of the same process. Thus , on the basis of the theory of Bekhtereva (1988) about the stable pathological state, it is reasonable to suggest that psychoactive drugs can cause destabilization of a functional state, which researchers mistake for a model of psychosis, and the dynamics of consciousness for an ASC. Such a suggestion may be supported by the comparison of different reactions of an organism to small versus high doses of the drug: small doses result in ASC versus high doses that result in extended clinical appearances of mental disturbance. It would probably be more justified to presume a combination of interconnection and difference of these two trends. The better elaboration of the first trend may be due to the fact that clinical effects of psychoactive drugs were observed and recorded by psychiatrists, with their professional inclination to regard as abnormal anything unknown in the mental reactions. The cause of such presumption could be the due to the peculiar inertia of scientific thought, which might considerably restrict research potential. However, the problem seems to be more profound and complicated. Psychoactive drugs meet the necessary requirements for scientific observation: their effects are reproducible, controllable by objective indicators, and predictable as a rule. As for ASC, no innovative methodologies have so far been proposed in this realm. Essentially, the comprehen277

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sion of psychoactive drugs is conditioned by the subculture, which has integrated them into its general outlook. As the latter is currently regarded in the framework of traditional psychiatry, no principally ncw generalizations can be expected as the peculiarities of the drug effect would invariably be attributed to the unusual pattern of a model psychosis. Nevertheless, if an alternative nonformal subculture could be found, another pattern - the ASC could gain momentum. American peyotism may serve as a suitable example. After a special structural analysis, Soviet ethnologists arrived at a conclusion that this is a religion with the necessary attributes, ethics, and rituals, although its axis is the use of peyote (Yevtukh 1985). Consequently, in conditions not burdened by connections with modem science, the use of peyote proceeded in accordance with most ancient religious patterns, including its integration into the society. The notion of a model psychosis would be improper here, while the assumption of ASC appears natural and justified. In concluding the discussion of the two basic trends in the research on psychoactive drugs, it would be constructive to discuss some intermediate conceptualizations, which are conditioned by such essential notions as constitution, personality peculiarities, and patterns of communication between the subject and the researcher. The present review article is unlikely to solve the problems arising here because there is another concept that is even more basic: the application of psychoactive drugs be gan before there was the elaboration of a suitable metalanguage for their description, including som e simple methodologies that could determine what the essence is of the effects of these drugs. Furthermore, attention needs to be given to the means of resolving this task. The main peculiarity of the Soviet tradition is that it was elaborated in clinical conditions, which is why a considerable part of its basic notions is not codified, being universally recognized, and used in practice . Thus, it is difficult for foreign colleagues to understand the implications and complieations of this tradition. In an attempt not to trespass the borders of general systems theory terminology, some guidelines are proposed. The framework of the early theorizing was that the combination of existing notions, or the mechanical addition of new ones, would lead to better insights into the objective evaluation of psychoactive drug effects. Both approaches were quickly realized . Consequently, psychiatrists attempted to describe the effects of psychoactive drugs in terms of a combination of traditional clinical syndromes (e.g., delirious, oneiric, depressive, schizophreniform) or they attempted to single out a special psychotoxic syndrome. In addition, an attempt was made to supplant the system of traditional terms by inserting methodologically (but not structurally) similar notions, such as "spectrum of individual psychotropic activity of a drug" and "psychopharJOUTnal of Psy choa ctive Drug s

macological profile of a drug " (Bobkov ct aI. 1984; Vinogradov, Spivak & Katkov 1982; Vinogradov & Spivak 1981; Valdman, Kozlovskaya & Medvedev 1979; Valdman 1976 ; Mashkovski 1974). Then an attempt was made to clearly single out instantly recogn izable and identifiable (suitable for quick prognosis) nontraditional categories and to incorporate them into clinical schemes of dynamics of drug effect. The developed schemes included the dose of the drug, the role of the psychological background of the subject, and/or the content of the mental activity during the period of action of the substance. The clinical picture of the influence of a drug on the psychological background of normals versus psychiatric patients indicates key differences. Thus, most characteristic for patients is either a fusion of symptoms of their primary disorder with the reaction to the substance (which results in states varying in symptoms) or the effa cement of the disease symptoms and the development of disorders that are monotonous in their manifestations. The former pattern of reaction is characteri stic for the derivatives of lysergic acid , and the latter for substances of cholinolytic effect. After the action of the psychoactive drug ceases, an easily observable pattern can be recorded along with its characteristic triggers (Anokhina 1975; Alcksandrovski 1958). There have al so been some constructive advancements in the study of the content of mental activity. It is worth noting that some interesting approaches in this direction were proposed as early as the second period. Here one finds such recently observed peculiarities of consciousness as alternating periods of clear consciousness with periods of unconsciousness and/or periods of consciousness of a different content (Kostandov 1983) . In the latter case, the extension of periods of the so-called gaps of consciousness (Kosmolinski 1976) could be supposed, forming a background for episodes of consciousness content irreducible to ordinary life impressions (Megrabyan 1959). In this respect, alterations of the processes, which have been described by Russian philologists as "chronotopos" (chronos=time , topos=place) for the purposes of scientific terminology, might take place. An example of this would include the individual re structuring of one's perception of time, space, personality limits, body scheme, and the volume of processed variants of behavior. In this context, methodologies for evaluation of the personal thresholds of perception and methodologies of ethology form a solid basis for research and description . Thus, the concept of action of psychoactive drugs may be designed from a balanced combination of trad itional (mainly theoretical) and nontraditional (mainly practical) notions. There is no doubt that researchers are stilI far from its true formalization. The present author has managed to 27 8

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approach some aspects of such formal ization only on the level of formal description of di fferences between two groups of psychodysleptics: LSD and glycolates (Milshtein & Spivak 197 1). This description seems possible within each of the two groups, following the introduction of some additional secondary limitations. As regards ASC, Soviet advances in this areaare more considerable than is reflected by the Western scientific literature. It was Ronchevski (1941) who described ASC as a feature of the effect of psychoactive drugs - similar to their dimension and devoid of traditional analogues - and introduced the notion of "mescaline alteration of consciousness." He wrote that " the available descriptions of mescaline alteration of consciousness are unsatisfactory, as they are deprived of concrete content ... such alteration of consciousness marked on the one hand by complete self-control, and on the other by inhibition of higher intellectual processes and enforcement of activity, producing and reproducing image experiences, should be most rcasonably called structural alLeration of cons ciousness .. ." distinguishing them in principle from any "confusion" of consciousness. He was succeeded by a number of researchers who found that subLlealterations of consciousness were difficult to qualify (e .g. , Raikov 1987; Davidenkov 1%3). In the course of the past 60 years , Soviet scientific literature has tended to emphasize the possibility of an intimate connection between artificially induced ASC and creative mechanisms (Karpov 1926): " ... [hu]mankind docs not possess means, which could enable it by its own wish to be plunged into a state of creative, intuitive processes ... usually in chasing the creative process the [person] resorts to strong Lea or coffee, and further to alcohol, morphine, hashish." Another problem usually omitted by scholars seems worthy of discussion: researchers often base their observations on the self-accounts of persons under investigation. However, up to now it has never been shown if the conceptual framework of the subject coincides with that of the researcher. The present author's experience of communication with people in an ASC testifies to their expression of thoughts and emotions in an idiosyncratic way, slighLly restructured in comparison with their normal everyday style. Moreover, having begun to mimic the lexicon and grammar of their speech, the present author invariably observed the improvement of the communication. As consciousness is inseparably linked with speech, it is necessary to demonstrate, before analyzing the selfaccounts of subjects in ASC, that the subjects are adequately understood. This leads, as a logical consequence, to the linguistics of ASC. Having formulated this objective, the present author has attempted to realize it in his investigations. The following methodology proved to be JOIUNJI ofPsychoactive Drugs

very promising. A short test was constructed whose structure and development were aimed at the answer to one major question. Has language structure altered qualitatively in comparison with the preceding state or not? In cases of such qualitative alteration, a tentative grammar and phrase book were constructed, with the latter be ing used in practical communication. As for the test, it was based on the traditional approaches of Russian linguistics (D.L. Spivak 1986) and was applied consequently and repeatedly before, during, and after the action of the psy choactive substance. The test was applied to study the action of cholinolytics, tranquilizers, insulin, atropine, and barbiturates (atropine and barbiturates were administered in combination with other drugs). This is why it would be premature to speak about any definite regularities of language structure induced by psychoactive drugs. However, it was found by D.L. Spivak (1986, 1983) that in the action of each drug studied there occurred a stage when definite qualitative shifts were indicated by the test (i.e., when variations appeared) . In cases of atropine or barbiturate administration, it was observed at the moment of tran sition from in itial to moderate effect of the drug. In this way the general viability of such an approach was suppo rted . It was the linguists who revealed positive interest in this approach for a scientific audience. In fact, the linguistics of ASC were presented at the International Congress of Linguistics held in Berlin during 1987 . It is the hope of the present author that this work will also be of interest to psychiatrists, psychologists, and physiologists. CONCLUSION The present author's general conclusion is optimistic: construction of a nontraditional language for the description of psychoactive drugs is possible. It is the present author's belief that its considerable components will be able to be constructed within the next decade. It is hoped that the present author has managed to demonstrate in this review article that, against the background of essential commonality in their approach to psychoactive drug research, the Soviet and the American research traditions concerning this topic reveal a fair degree of difference. Consequently, comparative research is not only possible but it is interesting and essential. The purpose of such research is undoubtedly humanistic in respect to both of its aspects: the traditional one, which is the development of the future theory of psychopharmacological therapy for patients, and the nontraditional aspect, which is the understanding of the psychopharmacology of normal human beings during ASC (Spivak, Raiski & Vilenski 1988; Bobkov & Vinogradov 1982). It is hoped that the present article will contribute to 279

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ACKNOWLEDGMENTS

a new and constructive branch of scientific connections. In the methodology of its development it would be wise to adhere to the opinion of Krippner (1986) who wrote that it is the".. . emphasis on the depths of consciousness that marks both Soviet and American psychologists who investigate hidden reserves and human potentials."

The author wishes to express his gratitude to Stanley Krippner, Ph .D ., Professor of Psychology, Saybrook Institute, San Francisco, and to the pragmatic efficiency of the Soviet-American exchange program of the Esalen Institute directed by Michael and Dulce Murphy.

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