PHARMACODYNAMIC ACTIVITY OF SMALL DOSES OF KETAMINE HYDROCHLORIDE (PARKE-DAVIS) ON THE PSYCHIC SPHERE

[Experimental research on 63 neurotic and/or psychotic-like cases]

§1. The experimental use of small doses of ketamine hydrochloride as an adjuvant psychotherapeutic agent in 63 cases revealed new dimensions of pharmacodynamic activity on the psychic sphere, completely contrary to the information given by Parke-Davis's prospectus about this drug.
§ 2. The prospectus for ketamine hydrochloride states, among other things, that it is used as an anaesthetic agent for diagnostic and surgical purposes in doses of 10 mg per kg body weight intramuscularly and 2 mg per kg body weight intravenously.

According to the prospectus, the pharmacodynamic activity of ketamine on the psychic sphere is characterised by:

• vivid dreams either pleasant or unpleasant with or without psychomotor activity.
• a state of confusion and
• irrational behaviour.

The above symptoms and phenomena appeared only during the stage of waking from the deep general anaesthesia brought about by ketamine, and for this reason they are labelled "emergency delirium" and regarded by the person who wrote the prospectus as constituting an "adverse psychological reaction."

I believe that I would be justified in asking the scientific director of Parke-Davis: By what criteria were the above patient reactions characterised as an adverse psychological reaction and irrational behaviour? The motive behind this question would be the subjective conclusions of the 47 patients (out of 63) whom I submitted to deep pharmaceutical psychotherapy sessions with ketamine hydrochloride. The conclusions in question were in total contrast to the contents of the prospectus - in the psychic sphere - as the reader will see in the following pages.

§ 3. Methodology of the present experimental research in 63 cases.
It is emphasised at the outset that the methodology of the present research is diametrically opposed to Cartesian "scientific" methodology and that its conclusions are based exclusively on patients' subjective experiences, on their personal conclusions regarding the content of their unconscious, the motivation for their morbid behaviour and the therapeutic results of the sessions with ketamine hydrochloride.

Selection of cases: The selection of the 63 cases, 32 women and 31 men, aged between 18 and 44 years old, was made from among the patients in my private practice who were suffering from neurotic or psychoticlike symptoms and phenomena. No patients with permanent psychotic symptoms were included in the group of 63. These 63 cases underwent deep pharmaceutical psychotherapy sessions with a view to improving their clinical condition or curing their neurotic or psychoticlike symptoms and phenomena. As an adjuvant pharmaceutical psychotherapy agent, ketamine hydrochloride was used.

Of the 63 cases, 47 successfully completed (see paragraph...) the scheduled number of autopsychognosia sessions. Also, clinical improvement or clinical cure (see paragraph ...) was achieved. There were 14 cases in which the sessions were stopped for reasons referred to in paragraph ...

The mode of use and dosage of ketamine hydrochloride: The ketamine was administered either intramuscularly or subcutaneously--never intravenously--in doses of 0.6 to 1.6 mg per kg of body weight.

Preparation for the ketamine sessions would begin with a questionnaire on the case history to which each patient would respond in written form. This was followed by two free communication sessions during which the patient was informed of the causes of the resistance developed during the ketamine sessions which inhibited the process, with the result that emotional realisations were not achieved in respect of the content of the unconscious and the motives of behaviour.

The above-mentioned preparation was followed by:
First Session: dose of 0.6 mg per kg of body weight
Second Session: (one week after the first) dose of 1 mg per kg of body weight.
Third Session: (one week after the second) dose of 1.2 mg per kg of body weight.
Fourth Session: (two weeks after the third) dose of 1.35 mg per kg of body weight.
Fifth Session: (two weeks after the fourth) dose of 1.45 mg per kg of body weight.
Sixth Session: (two to three weeks after the fifth) dose of 1.5 mg per kg of body weight.
Seventh Session: (two to four weeks after the sixth) dose of 1.5 to 1.6 mg per kg of body weight.

After the seventh session, there were another three with about 2-4 weeks in between each one. Dose: 1.5-1.6 mg per kg of body weight.
Note: Certain patients underwent more than ten sesions because they wanted to penetrate to deeper levels of the unconscious.

Each session with ketamine lasted for about 2-3 hours. Between ketamine sessions, there would be one free communication session to recapitulate the content of the previous sessions. This process made things much easier and was very effective because the sessions were taped.

The basic principle which was followed to the letter during the sessions with ketamine and the free communications was that I systematically avoided guiding or planning the sessions or suggesting any interpretation as to the content of the unconscious and the motivation of behaviour. These things were realised gradually, spontaneously and on an emotional level by the patients themselves, as long as they could externalise their every thought or emotion or visual image or, in general, whatever they felt during the ketamine sessions.

§4. Subjective experiences and emotional-intellectual realisations from 47 cases (out of the 63) during ketamine ydrochloride sessions.
The limited space in the present paper does not permit a detailed description of the experiences and the content of the Sessions; nonetheless I am bound to emphasise that a ketamine session is a very complex memory process during which experiences can be relived, mainly those of the distant past, with very strong emotional and physical synchronisation, i.e. the body subjectively takes on the dimensions which it had at the time of the remembered experience and relives intensely the feelings that accompanied it. There is also a noteworthy, strong kinetic- physical reaction that usually occurs during the relived experience. Below is a summary of the main experiences and the most significant conclusions which helped the patients to feel and understand emotionally the development mechanism of their mental disturbance and the motives for their everyday behaviour.

Foetal experiences (intrauterine) left memory traces which were preserved in the body after the patients' birth. The reactivation of these memory traces resulted in their reliving intrauterine experiences.
There are two types of foetal (intrauterine) experiences:
[A] Rejecting (= rejecting Womb) which are caused by:
(a) Emotional rejection of the existence (presence) and/or sex of the foetus on the part of the woman in whose womb it was growing.
(b) Emotional disturbances of the pregnant woman unrelated to acceptance or rejection of the foetus e.g. disastrous events in the external environment which upset the pregnant woman, such as the death of a loved one, financial disasters, wartime conditions, rape, etc.
The intrauterine rejection of the foetus by the womb- mother created in the foetus terrible fear = primitive terror.

[B] Accepting (=accepting Womb): caused by the emotional acceptance of the existence/presence and sex of the foetus on the part of the woman within whose womb it was developing. Accepting experiences are accompanied by a feeling of bliss and serenity. However even the accepting womb ultimately rejects the foetus during expulsion-birth.

Other factors which can cause primitive terror:

• Expulsion-birth
• Reactivation of rejecting memory traces inherited from ancestors.
• Rejecting stimuli from daily life which reactivate rejecting memory traces.
• Sexual activity which reactivates intrauterine rejecting memory traces.

On an unconscious level, sex symbolises the return to the womb. Sexual activity may possibly reactivate rejecting or accepting memory traces of intrauterine experiences.
-If accepting memory traces are reactivated, the sexual act is accompanied by a feeling of cosmic union.
-If rejecting intrauterine memory traces are reactivated, the sexual act is problematic because it tends to reactivate the hell of the rejecting Womb.

In daily life, it is possible for the memory traces of rejecting intrauterine experiences to be reactivated resulting in the feeling of very intense physical and mental hardships, the cause of which becomes understood only with the help of autopsychognosia sessions.

The foetus has the subjective feeling that it is surrounded by "something" colossal and all-powerful. After the generation of the memory traces of this "something" it is possible for them to create in the R a mystic impression of the existence of a supernatural power. (see p...)
Note: each of the 47 patients in question relived one or more experiences similar to those described above.

§5. Sessions with ketamine were discontinued in 14 of the 63 cases:
(a) A young man of 19 years old decided to discontinue the Sessions after the first one, and a woman of 30 after the sixth one because during the Sessions, these patients were both overcome by intense, near-panic fear. They stated that it would be unbearable for them to realise the cause of their fear. Thus they had blocked the process of the Sessions, focusing their thought on irrelevant matters.
(b) Five other cases: four women 18 to 27 years old and a man of 29 discontinued the Sessions between the first and the fifth since they could not externalise to the supporting doctor the ideas which were going through their minds.
(c) Three men, 22, 26 and 28 years old, underwent 10 sessions during which they remained silent. In reply to my urging that they externalise what they were feeling they uttered monosyllables or said that they felt absolutely nothing.
(d) A man of 33 discontinued the Sessions after the sixth. During the first five, he felt fine. During the sixth he felt a terrible fear. When I urged him not to neutralise it, he reacted negatively.
(e) A 26-year-old man, after visiting my office for the first time, declared that he had decided to commit suicide since his life had become an almost constant feeling of mental and physical pain. At the same time, he engaged in homosexual activity which was for him psychologically unacceptable. His every effort to explain his own feelings and behaviour ended in a confusing impasse. As a final effort he wanted to try ketamine sessions which one of my patients had told him about. This man went through eight sessions during which the following image-feeling was repeated many times: he felt that he was in an oven and that flames were burning him, turning him into a charred foetus. Strong hyper-kinetic movement and terrible cries accompanied the image-feeling. The interpretation given by the patient himself is worthy of note: Oven = Womb. Flames = rejecting uterine messages. Charred foetus = that which should have happened in the womb. After the eighth session I had to make a trip abroad. Upon my return to Athens I was informed that the patient had committed suicide in the following manner: he had poured alcohol over his body and set himself alight.
I believe that the following two cases are significant:
(a) A woman 23 years old went through 12 sessions. She herself was highly satisfied until the eleventh. During the 12th she experienced sexual desire for her younger sister. After the 12th she rejected the content of all Sessions as analysed.

(b) A man of 30 underwent 10 Sessions during which he relived psychotraumatic events from his childhood. He did not relive intrauterine experiences nor experiences of expulsion- birth. This patient showed clinical improvement after the ketamine sessions.

§6. Therapeutic results of ketamine sessions.
Based on the subjective judgement of each of the 63 cases:
12 showed slight improvement in their mental disturbance
17 showed moderate improvement in their mental disturbance
7 showed moderate to significant improvement in their mental disturbance
12 showed significant improvement in their mental disturbance 14 showed no change in their mental disturbance
Note 1: follow up period: 2 to 8 years
Note 2: about the person who committed suicide, see above (paragraph e.)

§7. Discussion
With respect to the symptoms and phenomena of ketamine hydrochloride on the psychic sphere, the diametric contrast between the explanations given by the Parke-Davis prospectus on the one hand and by my 47 patients on the other is undoubtedly impressive.

The prospectus does not hesitate to describe the side- effects of ketamine on the psychic sphere as being unpleasant. Unquestionably this description will make the doctor who might wish to use ketamine hesitate to do so.

On the other hand, my 47 patients not only interpreted the development mechanism of the symptoms and phenomena in question but also felt that their mental health improved after the ketamine sessions.

From a general point of view, the fact that the prospectus describes the side-effects of ketamine as being unpleasant was regarded by the 47 patients as being a result of reliving experiences from their distant past. More particularly:

• The "pleasant" dreams were the result of reliving accepting intrauterine memories.
• The "unpleasant" dreams were the result of reliving rejecting intrauterine memories. The strong psychomotor reaction that accompanied the "unpleasant" dreams was the result of the R's emotional and physical reaction to the fear caused by his rejection by the woman in whose womb he was growing.
• The "confusing" state was the result of the simultaneous reliving of events and experiences which had taken place at different periods in the past.
• The "irrational" behaviour was not at all irrational but, on the contrary, was most "appropriate" in order to confront the terrifying rejecting womb.

§8. It is obvious that fear constitutes the primary motive not only for morbid but also generally for the ordinary behaviour of the patients in the present experimental research. It was thus inevitable that its conclusions would be based exclusively on subjective experiences, on subjective conclusions and subjective reactions on the part of the patients in question, since creating the objective criteria of fear is not feasible.

Those who reject the present research on the grounds that it disregards the principles of Cartesian "scientific" methodology, are referred to the thoughts and speculations of mathematical philosophers and natural philosophers such as Mach, Russell, Godel, Schrodinger. Although they used Cartesian methodology successfully in the realm of science, this did not prevent them from speculating on the subjectivity of matter (or from believing that this subjectivity constitutes a basic feature of matter). It is noteworthy that the philosophers in question do not tell us anything new. In the 7th century BC, the Milesian philosophers, the greatest philosophers of all times, espoused the principle of the subjectivity of matter declaring that matter is inseparable from the spirit, that animate and inanimate creatures are made of the same basic material and that everything has a universal unity.

To those who persist in the Cartesian "scientific" methodology I would submit the following questions:

• With what objective criteria and with what laboratory research methods can traditional psychiatry diagnose and classify mental disturbances?
• How objective is the opinion of the psychiatrist who diagnoses a mental disturbance? Has this opinion or has it not been shaped by his subjective experiences and by subjective problems? How objective are the criteria of traditional psychiatry which shaped his psychiatric knowledge? Is it or is it not the description of the clinical picture of mental disturbances based on the patients' subjective experiences as they themselves describe them during the psychiatric examination?
• What are the objective criteria on which Freud based the principles of psychoanalysis?
• With what objective criteria do psychotherapists conduct psychotherapy on their patients?

The replies to the above questions should be able to stand up to the criticism of the absolute sense of the term "objective criterion".

§9. I regard the suicide of the 26-year-old man (paragraph ...), as being an inevitable consequence of the unceasing reactivation of the memory traces of his intrauterine rejection in everyday life. Setting fire to himself was a replication of the intrauterine process of "burning" by the intrauterine rejecting messages.

§10. A theoretical interpretation of the process of the ketamine hydrochloride session: The very vivid reliving of experiences and events of the past with physical and emotional synchronisation during a ketamine hydrochloride session can be interpreted theoretically as follows:

Events of the past and the emotional processes which accompany them leave memory traces in human cells. These memory traces are preserved in a latent state and some of them are transmitted to descendants through heredity.

The primary pharmacodynamic activity of ketamine hydrochloride in the psychic sphere is the reactivation of these memory traces. Intense reactivation can cause the vivid reliving of experiences and feelings from the past (the recent, distant and even ancestral past) and a very strong psychomotor reaction, particularly when rejecting intrauterine experiences or the birth trauma are being relived.

§11. It is emphasised that the person to whom ketamine is administered in a dosage of 0.6 - 1 mg per kg of body weight (i.e. the dose of the first and second session) can neutralise its pharmacodynamic activity fully. One frequent cause of such a neutralisation is the great intensity of the fear which derives from reliving terribly painful experiences of the past. Of course by neutralising the drug, the patient discontinues the process of emotional and intellectual realisations.

BIBLIOGRAPHY

A. Kafkalides, The Knowledge of the Womb
R. Rucker, "Discussion with Godel", in Infinity and the Mind
B. Russel, "Philosophy of the Twentieth Century", in Problems of Philosophy
Schrödinger, Science and Humanism