Art. Krupitsky Grinenko - formula

Ketamine Psychedelic Therapy of Alcohol dependence

  • by Evgeny M. Krupitsky & A. Ya. Grinenko
Originally published on Eleusis, n. 4, pp. 18-29

Psychedelic psychotherapy was shown to be a potential benefit for alcoholism treatment in the "60s", but different methodologies made it difficult to generalize across studies. It was not possible to carry out the required development of appropiate sophistication for these studies after they were scheduled in 1970 and their use was strictly limited. However, at about this time, ketamine was shown to elicit "psychedelic" emergent phenomena in patients. This property of ketamine was exploited by our use of ketamine-assisted therapy of alcoholism. Ketamine has some advantages over other psychedelics as an adjunct to psychotherapy. It is safe and short acting (the psychoactive effects lasting about one hour). In addition, ketamine is not scheduled like other psychedelics. In lower doses (about one sixth to one tenth of that usually used in surgery for general anaesthesia) it induces a profound psychedelic experience.

In our model psychotherapy consists in the preparation of a patient for the psychedelic session, the psychotherapeutic facilitation of the session, and special post-session psychotherapy (Krupitsky, 1992). This post-session work is intended to help the patient integrate insights from the psychedelic experience to daily life and relate the experience to his life and personality problems. Moreover, in this way psychotherapy acquires a special quality. It is considered here not only as a process of resolution of certain psychological problems, but also as an important stage in spiritual maturation. The uniquely profound and powerful psychedelic experience often helps our patients to generate new insights that enable them to integrate new, often unexpected meanings, values and attitudes about their individual selves and the world.

We carried out a controlled clinical trial on the efficacy of KPT. To determine the efficiency of the treatment, we collected follow-up information about all the patients who had taken part in this study a year after their discharge. According to data, abstinence of more than 1 year was observed in 73 out of 111 people (65.8%) who had undergone the KPT. Thirty people (27.0%) had relapsed. We could not obtain data on eight patients (7.2%). In the control group of 100 patients whose treatment consisted only of conventional methods, only 24 patients (24%) remained sober for more than 1 year. Thus, the data from the follow-up study demonstrated that ketamine-assisted psychedelic therapy increases the efficacy of conventional alcoholism treatment.

Two-year follow-up data were collected for the 81 patients who had undergone the KPT (because at the moment of the follow-up study only 81 out of 111 patients had completed the two-year follow-up period after KPT). According to data, abstinence of more than 2 years was observed in 33 out of these 81 patients (40.7%). 38 patients (46.9%) had relapsed. We could not obtain two-year follow-up data for 10 patients (12.4%). Three-year follow-up data were collected for the 42 patients who had undergone KPT. According to data, abstinence of more than 3 years was observed in 14 out of these 42 patients (33.3%). 24 patients (57.2%) had relapsed. We could not obtain three-year follow-up data for 4 patients (9.5%). The two- and three-year follow-up data are also evidence of the high efficacy of KPT.

We also carried out studies on the different underlying mechanisms of KPT: psychological, biochemical, and neurophysiological mechanisms.

Underlying psychological mechanisms


All patients of the experimental group were examined with the Minnesota Multiphasic Personality Inventory (MMPI) (adapted in Russia by Sobchik, 1990) before and after KPT.

According to MMPI data, our analysis of psychological changes in the experimental group testifies a definite, rather expressed dynamics in the patient's MMPI profiles. Particularly, after the KPT the indices were decreased for the majority of the main MMPI scales. The most expressed, statistically significant decrease in the profile was in the scales "hypochondria", "depression", "hysteria", "psychastenia", "schizophrenia", "sensitivity-repression", and also in Taylor's scale of anxiety. At the same time, the estimate in the Ego strength scale increased. On the whole, such favorable psychological dynamics testify the fact that the patients became more sure of themselves, their possibilities, their future, less anxious and neurotic, and more emotionally open after KPT. Against the background of these general tendencies, in the majority of cases we saw some essential individual variations (e.g. concerning changes in such scales as "masculinity-femininity", "paranoia", "hypomania", "sensitivity-repression") that reflected, as a rule, a certain harmonization of the patient's personality profiles.

Locus of Control

30 alcoholic patients treated by KPT were examined with Locus of Control Scale (LCS) developed by J. Rotter (Phares, 1976) and adapted in Russia by Bazhin et al. (1993). All patients were assessed with LCS twice: before and after KPT.

It was established that locus of control in the personality of alcoholic patients became significantly more internal after KPT (from 11.1 ± 4.8 to 30.3 ± 5.3; P < 0.01). It means that patients became more sure about the ability to control and manage different situations of their life, they became more responsible for their life and future after KPT.

Psychosemantic Changes. A study with Color Test of Attitudes and Personality Differential

We also studied changes in the psychosemantic domain induced by KPT. The study used data from 69 alcoholic in-patients treated by KPT in our hospital. All patients were examined using the personality differential test (PD) (Bazhin & Etkind, 1983) (a personality oriented version of Osgood's semantic differential (Osgood et al., 1957), and also using the color test of attitudes (CTA) (Etkind, 1980) before and after treatment.

The analysis of the CTA results revealed that after KPT there were significant positive changes in the nonverbal emotional attitude towards a psychotherapist, close relatives, towards the ideal image of self, and the image "Me sober". At the same time, the attitude towards the image "Me drunk" became more negative. According to the PD data, significant positive changes occurred after KPT only in respect to the attitude toward the person himself (Krupitsky, 1992).

After KPT there was a considerable decrease in differences between the certain indices of CTA and that of PD with respect to the same images. This decrease evidenced the reduction of the difference between the verbal (realized) and nonverbal (unrealized) assessments of personal attitudes. Such reduction was mainly related to the change in the CTA indices and appeared to be the strongest for the sphere of attitudes towards a psychotherapist, relatives, the image "Me sober", and the ideal image of self.

Thus, the KPT produced considerable and significant positive changes in the domain of personality attitudes, which took place due to the transformation of nonverbal (unrealized) emotional attitudes. KPT resulted in a decreased level of dissonance between isosemantic indices as measured by CTA and PD. This could be interpreted as a reduction of dissonance between verbal/conscious and nonverbal/unconscious thoughts and feelings regarding alcohol use and personality characteristics and relationships.

One should underline the fact that, according to the CTA data, there were strong positive changes in patients' nonverbal (unrealized) assessments of the attitudes towards a psychotherapist, close relatives, to the image "Me sober", and to the ideal image of self. This means that the patient has internally grown to emotionally accept these images and, in turn, the attitudes towards sobriety connected with them. Thus KPT of alcoholism may be of benefit by transforming unconscious attitudes, particularly those related to sobriety. Also the enhancement of the relationship with the therapist may have enhanced transfert issues which may also have had a therapeutic effect.

A special note should be taken of the discrepancies between the verbal and nonverbal estimate of patients' personal attitudes registered before KPT. These discrepancies, obviously, reflect the presence of an essential discordance between the conscious and unconscious estimates of a personality's attitude. This discordance reflects a peculiar difference between the subject's unconscious and conscious mind. It possibly characterizes the ambivalence of the patient's position and the disagreement between what is declared verbally and what takes place at the level of the immediate emotional experience. Such discordance may give rise to psychological discomfort, internal tension, difficulties in communication with the environment, i.e. to the reduction of a person's adaptation, which after all leads to the alcoholism relapse. Therefore, the reduction of such discordance due to KPT should be considered as an achievement of a personality's psychological status which favors sobriety.

A study with repertory grids (Kelly matrixes)

Ten alcoholic patients were tested with verbal and special nonverbal (color) repertory grids before and after KPT. Then we calculated mean verbal repertory grid (MVRG) and mean color (nonverbal) repertory grid (MCRG) for all the 10 patients together. Four final MVRG and MCRG (2 before KPT and 2 after KPT) were processed by the standard programs of repertory grid computer-assisted analysis (Fransella & Bannister, 1977), and then semantic spaces of the personality were built (Figs. 1 and 2). Semantic space of the personality (built on the basis of multidimentional assessments of elements with constructs) shows semantic interelationships and interconnections between elements and/or constructs of repertory grid.

The results of this study demonstrated some positive changes in the semantic space of the personality of alcoholic patients, particularly in the space of personality characteristics of the color repertory grids. The image "Me now" was close to the image "Drunkard" and far from the group of such positive images as "Recovery alcoholic", "Ideal image of self", "Wife", "A man who gets on in life", and others in the semantic space of the MCRG before KPT (Fig. 1a). After KPT the image "Me now" became closer to the group of positive images described above and far from the image "Drunkard" in the space of MCRG (Fig. 1b). At the same time the image "Drunkard" became closer to the image "Me in the past". These data testify that alcoholic patients emotionally perceived (identified) themselves as drunkards before KPT. After KPT their emotional perception of themselves was changed: they emotionally identified themselves with recovery alcoholic and other positive images in the semantic space of personality characteristics and value orientations, and identified themselves as drunkards only in the past.

The changes in the verbal repertory grids were not as significant as in the color repertory grids (Fig. 2a and 2b). Only the image "Drunkard" became a little bit more distant from the group of positive images and closer to the image "Me in the past". It is interesting to note that patients identified themselves with the positive images at the level of verbal self-identification in the semantic space of personality characteristics and value orientations already before KPT, whereas they identified themselves in the same way at the level of nonverbal (unaware, mostly emotional) perception only after KPT. That means, first, that KPT creates a profound nonverbal state associated with sobriety self-concept, and second, that KPT brings about the attainment of similarity (resemblance) of verbal (realized) and nonverbal (unaware) perception by the patients of their individual self and the world.

These data testify that KPT positively transformed mostly the nonverbal (unaware, mainly emotional) perception by alcoholic patients, their individual self. Thus, it is possible to conclude that KPT mostly transformed positively emotional self-identification (self-concept) of alcoholic patients.

Content Analysis Data

We also carried out content-analysis of psychedelic experiences written down by our patients after their KPT session. It is of interest to note that a content analysis from the written self-reports of 108 male alcoholic patients whose personality characteristics were defined by MMPI demonstrated a number of statistically reliable correlations between some MMPI scales and the content of the psychedelic experience described in self-reports. Thus one may conclude that the ketamine psychedelic experiences are to a certain extent determined by the personality characteristics of the patients.

In addition we also demonstrated the relationship (statistically reliable correlations) between the content of the ketamine session experiences and the MMPI profile changes caused by KPT. It means that the content of the ketamine session experiences to a certain extent determine the personality changes caused by KPT.

Effect on Life Values

30 patients assessed with LCS were also examined with the Questionnaire of Terminal Life Values (QTLV) developed by Senin (1991) and based on the Rokeach's approach to human values and beliefs (Rokeach, 1972, 1973). Patients were examined twice with QTLV: before and after KPT.

This study demonstrated a number of significant positive changes in patients' values as a result of KPT. KPT enhanced the importance of such life values as creativity, self-perfection, spiritual contentment, social recognition, achievement of life purposes and individual independence. These changes were mostly expressed in areas of life values actualization such as family, education and social life. It is evident that such a positive transformation of a patient's life value system brings about an enhanced motivation for a sober life and favors sobriety.

Effect on grasping the meaning of life (purposes in life)

Ten alcoholic patients were studied before and after KPT with the Purpose-in-Life Test (PLT) elaborated by Crumbaugh (1968) and based on Frankl's concept of man's aspiration for the meaning of life. The PLT was adapted in Russia by Leontiev (1992) in the Department of Psychology of the Moscow State University.

This study showed that KPT causes a significant increase of the index of grasping the meaning of life in alcoholic patients (from 89.7 ± 5.7 to 115.3 ± 3.2; P < 0.01). Before KPT this index was below the average normal level, but after KPT it was above that level. These changes mean that after KPT patients were able to grasp better the meaning of their lives, their life purposes and perspectives. Life became easier in accordance with their concept of the meaning of life and life purposes as a result of KPT. Such changes favor a sober life particularly from the standpoint of Frankl's approach which considers alcoholism as an "existential neurosis", a consequence of losing the meaning of life and appearing a specific "existential void" (Frankl, 1978), which KPT we believe is able to fill at least to some extent.

Effect on Spirituality

We studied the influence of a profound mystical (transformative) experience during the KPT on the spiritual development of the alcoholic patients. For the assessment of the changes of spirituality we used our own special Spirituality Scale. It is based on the combination of the Spirituality Self-Assessment Scale developed by Charles Whitfield, who studied the importance of spirituality in alcoholism therapy in Alcoholic Anonymous (Wthitfield, 1984), and the Life Changes Inventory developed by Ken Ring to estimate the changes into values and purposes of life produced by near-death experiences (Ring, 1984). It was demonstrated by our Spirituality Scale that the increase in the level of spiritual development of our alcoholic patients due to KPT was comparable with the increase induced in healthy volunteers by a special course of meditation and was much greater then the changes in spiritual development induced in alcoholics by a training program of relaxation technique and selfhypnosis (autogenic training). It is evident that the increased spiritual development induced by KPT in alcoholic patients is very auspicious for sobriety. Moreover, the results of the study of KPT's influence on spirituality testify that KPT is much more than simply a creation of an attitude towards a sober life in alcoholic patients. These results serve as evidence that KPT brings about profound positive changes in life values and purposes, in the attitudes towards the different aspects of life and death, and, in turn, in the alcoholics' world view. Many reports suggest religious or spiritual conversions as an important factor in "spontaneous" recovery from common drug abuse, and Alcoholic Anonymous programs have a distinct spiritual/religious orientation (Whitfield, 1984; Corrington, 1989; Grof, 1990). Therefore a therapy enhancing the likelihood for a conversion type experience might be useful in the treatment of substance abuse. Psychedelic drug-assisted psychotherapy may represent one method to elicit religious spiritual experience in patients with chemical dependence.

Thus, KPT brings about positive changes in personality characteristics, nonverbal emotional attitudes and self-concept, positive transformation of value orientations and grasping the meaning of life, and also spiritual growth. All these psychological changes favor sober life.

Underlying Biochemical Mechanisms

We also carried out biochemical investigations of the underlying mechanisms of KPT. The results of the biochemical investigations showed that during the ketamine session there was a real decrease in the activity of MAO-A in blood serum and MAO-B in blood platelets, and also there was an increase of dopamine level in blood. Serotonin and GABA concentrations were not altered significantly. Increase of ceruloplasmin activity was statistically significant and the ß-endorphine level increased during the KPT session (Krupitsky et al., 1990).

The changes of the neurotransmitters metabolism have some notable aspects. First, they allow to understand something how the underlying neurochemical mechanisms of ketamine psychedelic action are formed (Krupitsky et al., 1990). For example, an increase of ceruloplasmin activity causes a corresponding increase of conversion of monoamines into adrenochromes wich have hallucinogenic activity. This is particularly important under the conditions of the inhibited MAO activity and increased dopamine level. It is interesting that such conditions be typical for the action of many hallucinogens (Hamox, 1984; McKenna et al., 1984).

Second, the fact that the pharmacological action of KPT affected both the monoaminergic and the opioidergic systems, i.e. those neurochemical brain systems which are involved in the development (pathogenesis) of alcohol dependence, is an important result of this biochemical investigation. It is possible that this fact influences the efficiency of this method at least to a certain extent.

Underlying Neurophysiological Mechanisms

According to the data of EEG computer-assisted analysis we discovered that ketamine increases delta-activity (in 1.5-2 times) and particularly theta-activity (in 3-4 times) in all regions of the brain cortex. This is evidence of limbic system activation during the ketamine session, as well as of the reinforcement of the limbic-cortex interaction. This fact can be also considered to a certain extent as indirect evidence of the strengthening of the interactions between the conscious and subconscious levels of the mind during the KPT.

Clinical observations

Our clinical observations also suggested that KPT might be helpful in the treatment of other drug dependences (heroin, ephedron). In this case we have repeatedly injected small doses of ketamine allowing the maintenance of a constant verbal relationship with the patient. It is important to be careful when applying KPT to drug addicts. However we believe that KPT might induce in some drug abusing patients the same psychotherapeutic effects that we saw in alcoholics.

Ketamine psychedelic therapy turned out to be effective for the treatment of personality disorders in alcoholic patients (Ivanov et al., 1995). 64 alcoholic patients with different personality disorders (avoidant - 20 patients, histrionic - 21 patients, and borderline - 23 patients) were treated with KPT. Data of clinical (Bekhterev Psychoneurological Research Institute rating scales) and psychological (MMPI, Spielberger State-Trait Anxiety Scale, T. Leary test of interpersonal relationships) studies showed the differential efficacy of ketamine psychedelic psychotherapy in the different groups of patients. KPT turned out to be very effective in patients with avoidant personality disorders, less effective in patients with istrionic personality disorders, and showed low effectiveness in patients with borderline personality disorders. It shoul be noted that KPT positively influenced the personality characteristics assessed by MMPI in all groups of alcoholic patients with personality disorders.

The potential of ketamine-assisted psychedelic therapy is not restricted to the treatment of addiction. According to data from our pilot study (20 patients, 7 male and 13 female), ketamine-assisted psychedelic therapy is also quite effective in treating neurotic disorders. This research demonstrated that the efficacy of ketamine psychotherapy differed in the various form of neuroses: psychedelic therapy turned out to be most effective in treating neurotic (reactive) depression and post-traumatic stress disorders, and least effective in treating obsessive-compulsive and phobic neuroses. Hysterical neurosis appeared to be most resistant to psychedelic therapy.


We have been working with KPT since 1985 and have already treated more than 1000 alcoholic patients with KPT without any complications like protracted psychoses, flashbacks, agitation, or ketamine abuse. So, KPT seems to be a safe and effective method of treatment for alcohol dependence. It seems to be an especially powerful tool in Russia, where there was no psychedelic "revolution" in the 60s, where almost nobody knows what "psychedelics" mean, where almost nobody can even imagine that these drugs can be used for recreation, and for fun, therefore in Russia KPT looks particularly unusual and powerful.


Bazhin E.F. & A.M. Etkind, 1983, A Manual for Personality Differential, Leningrad (in Russian).

Bazhin E.F., E.A. Golynkina & A.M. Etkind, 1993, Locus of Control Questionnaire, Symsl, Moscow (in Russian).

Corrington J.E., 1989, Spirituality and recovery: relationships between levels of spirituality, contentment and stress during recovery from alcoholism, Alcohol.Treat.Quart., 6: 151-165.

Crumbaugh J.S., 1968, Cross-validation of Purpose-in-Life Test based on Frankl's concept, J.Indiv.Psychol., 24: 74-81.

Etkind A.M., 1980, Colour test of attitudes and its use in the study of neurotic patients, in: E.F. Bazhin (Ed.), Social-Psychological Studies in Psychoneurology, :110-114, Leningrad Research Psychoneurological Institute, Leningrad (in Russian).

Frankl V., 1978, The unheared cry for meaning, New York.

Fransella F. & D. Bannister, 1977, A Manual for Repertory Grid Technique, Academic Press, London-New York.

Grof Ch., 1990, The impoverished soul: addictions as spiritual emergency, Spiritual Emergency Network J., 2: 20-29.

Hamox M., 1984, Common neurochemical correlates to the action of hallucinogens, in: Hallucinogens: Neurochemical Behavioral and Clinical Perspectives, 4: 143-169, Raven Press, New York.

Ivanov V.B., E.M. Krupitsky, E.N. Romanova, I.V. Dunaevsky & A.Ya. Grinenko, 1995, Ketamine psychedelic therapy of personality disorders in alcoholic patients, in: Abstract Book, 3 rd International Conference "AIDS, Cancer and Related Problems", p. 45, St. Petersburg.

Krupitsky E.M., 1992, Ketamine psychedelic Therapy (KPT) of alcoholism and neurosis, MAPS, 3: 24-28.

Krupitsky E.M., A.Ya Grinenko, G.F. Karandashova, T.N. Berkaliev, K.A. Moshkov & Yu.S. Borodkin, 1990, Metabolism of biogenic amines induced by alcoholism narcopsychotherapy with ketamine administration, Biogenic Amines, 7: 577-582.

Leontiev D.A., 1992, Test of the meaning of life orientations, Smisl, Moscow (in Russian).

McKenna T.D., G.H.W. Towers & T.S. Abbots, 1984, Monoamine oxidase inhibitors in South American hallucinogenic plants. Part 2. Constituents of orally-active Myristicaceous hallucinogens, J. Ethnopharm., 12: 179.211.

Osgood Ch., C.J. Susi & P.M. Tannembaum, 1957, The Measurement of Meaning, Urbana.

Phares E.J., 1976, Locus of Control in Personality, New York.

Ring K., 1984, Heading Toward OMEGA, William Morrow and Co. Inc., New York.

Rokeach M., 1972, Beliefs, Attitudes and Values, Josey-Bass Co., San Francisco.

Rokeach M., 1973, The Nature of Human Values, Free Press, New York.

Senin I.G., 1991, Questionnaire of Terminal Life Values, Yaroslavl (in Russian).

Sobchik L.N., 1990, Standardized Multiphasic Method of the Research of Personality, Moscow (in Russian).

Wthitfield C.L., 1984, Stress management and spirituality dyuring recovery: a transpersonal approach. Part 1: Becoming, Alcohol.Treat.Qaurt., 1: 3-54.


Fondazione MCR

Divulgazione scientifica, multimedialità e nuove tecnologie si intrecciano nelle attività quotidiane della Fondazione Museo Civico di Rovereto. La ricerca e la formazione, attraverso i laboratori rivolti alle scuole, rappresentano da sempre la priorità di uno dei musei scientifici più antichi d'Italia.


Iscriviti per ricevere la newsletter informativa sulle attività della Fondazione MCR