Ketamine Psychedelic Psychotherapy

KETAMINE PSYCHEDELIC PSYCHOTHERAPY

EVGENY KRUPITSKY AND ELI KOLP

INTRODUCTION

Ketamine hydrochloride is a general anesthetic which has been used for noncon- ventional applications in substance abuse rehabilitation because of its psychedelic properties. This chapter summarizes the results of the research on KPP (ketamine psychedelic psychotherapy), principally with alcoholics and heroin addicts. Mechanisms underlying the effects of hallucinogen-assisted psychotherapy are addressed. Research illustrates how the temporary but effective anti-addictive benefits for a short period of time can be extended for longer periods of time to improve overall long-term adjustment and level of functioning. Ketamine hydrochloride, a prescription drug used for general anesthesia, induces profound psychedelic experiences when administered in sub-anesthetic .doses. Ketamine was originally synthesized in 1962 by the American chemist Calvin Stevens, and in 1966 Parke-Davis patented it for use as an anesthetic in humans. Ketamine became the most widely used anesthetic during the Vietnam War when American anesthesiologists and surgeons became familiar with the agent. In 1970, the U.S. Food and Drug Administration approved the use of ketamine with children, adults, and the elderly. Since that time, ketamine has been widely used in hospitals and for office procedures because of its large margin of safety, rapid onset, and short duration of action. More than 7,000 68 TREATTNG SUBSTANCE ABUSE published reports describe ketamine's high level of effectiveness and its biological safety (Shapiro et al. 1972; Reich and Silvay 1989; Ross and Fochtman 1995; Dachs and Innes 1997; Bauman et al. 1999; Ersek 2004). Clinical studies have detected no long-term impairment of behavior or personality functioning as a result of ketamine use (Siegal 1978). According to several reports, ketamine actually prevents brain damage from strokes, head trauma, heart attacks, epileptic seizures, low oxygen levels, and low blood-sugar levels (Weiss et al. 1986; Rothman et al. 1987; Shapira et al. 1994; Hirota and Lambert 1996). A rapid-acting, nonnarcotic, nonbarbiturate agent, ketamine has been termed a "dissociative" anesthetic, as it appears to disconnect the mind from the body, unlike the action of conventional anesthetics that basically extinguish consciousness. This dissociati ve action of ketamine creates what is described as "emergence phenomena," a nonordinary state of consciousness during which the individual's awareness and perception are dramatically changed and radically refocused.The patient completely loses contact with external reality and gets involved in a profound psychedelic experience. This experience may include (Khorramzadeh and Lofty 1976; Moore and Alltounian 1978; Weil and Rosen 1983; Lilly 1988; Krystal et al. 1994; Krupitsky and Grinenko 1997):

• Feeling that one has left one's body (i.e., out-of-body experience); • Awareness of becoming a nonphysical being; • Emotionally intense visions; •Feelings of ego dissolution and loss of identity; • Visits to mythological realms of consciousness; •Reexperiencing the birth process; • Vivid dreams and memories of past incarnations; • Encounters with archetypal beings; • Experience of psychological death and rebirth of ego; •Feelings of cosmic unity with humanity, nature, the universe, and God.

A profound psychedelic experience lasting from 45 minutes to an hour is induced by doses of ketamine about one-sixth to one-tenth of that typically used in surgery for general anesthesia. The following self-reports describe the details of the KPP experience that profoundly affected three selected patients:

Patient A.S.: Sticky masses began to attack my body, to melt it. Fear invaded me. Every- thing around was in a whirl. One thing overlapped another. I felt the odor of alcohol. I felt excruciating aversion, fear, and presentiment of death. Bright objects replaced one another at a crazy speed, everything went round, and I went round, too. It seemed to me that I would never get out of this nightmare; that I was slowly and painfully dying; that I, my entire self, would melt in this black mass, but my brain would go on working. That I would feel, think, not live, but suffer. ...Some voice was talking about alcohol; I felt a strong aversion .... KET AMINE PSYCHEDELIC PSYCHOTHERAPY 69

Everything I saw resulted from my hopeless life, my alcoholism. It was as if the trash accumulated in me during years and years went out of me during an hour. I do not want it to repeat; I am afraid of this nightmare .... I would never forget it. ."

Patient S.K.: I felt that my legs did not move, and my body started stretching and falling down at a crazy speed. My consciousness concentrated at one point and became a part of the scene. I was flying to infinity along something like channels that interlaced and joined one another (everything was brightly colored: orange, red). Gradually, this crazy dance grew slower. I found myself in some closed space. At that moment an unconscious fear invaded me. Fear that I would never get out of this state-the state of being a part of something and not myself. The space where I was started filling with solid foam. I was cornered. At the last moment, when I saw that I couldn't get away, that the space I occupied was the only free spot, I heard something splash and felt myself free. Everything around became understandable (I thought that it was impossible to live the way I had lived). My family came distinctly to my mind .... Now it was as if my consciousness was over the things that were under me. Everything below looked like some brown layers: as if a clot of brown dough scattered in the air and came down to the earth and covered it all over. It seemed to be my past life. Again, a strong fear overwhelmed me as I was pulled to this brown mess. All my self rose against it. I deeply desired to live, to live as everybody else, and never see this nightmare again. And my desire won. At this point, I felt as if I opened my eyes and regained my sight. I saw a window, a green tree and the blue sky .. "

Patient V.K.: As soon as I had been brought to the state of unconsciousness, I started slid- ing in a curve of the vertical plane. The latter was distinct and represented a blue line against the clearly visible and illuminated background. The thought: some- where there is a point which is important for you, which you should not miss, since it is a matter of life or death. I slid for a quite a long time, but I never met this point. Abruptly I found myself in a cave on the top of a high granite rock .... The rock rose high above the ocean that exactly resembled the thinking ocean of (Stanislaus) Lem's 'Solaris.' The ocean was brownish-crimson, swirling, and looked like the upper parts of cumulus clouds, as seen from an airplane before the sunset. The cave had an entry which without any reason seemed black. The ocean was several hundred meters below the cave, and I could distinctly imagine that sooner or later I would fall down and it would swallow me up. I didn't feel my body, but in the cave some ellipse-shaped, orange concentrate of thoughts, my thoughts, was pulsating. The thoughts were: the universe is infinite in space and time; we are all mortal; the space, the ocean will always be, but thoughts will die and nonexistence will come .... I felt hopeless and was surprised only at one thing: why the thought to live persists, to live endlessly. Several scenes of my life 70 TREATINGSUBSTANCE ABUSE passed before my eyes. They were from my childhood and youth, everything in sad, reddish-brown colors. Several times the thought, but not the body, appeared at the exit ofthe cave and I could understand that I was about to fall down into the ocean, but I would not fall down and again would return into the cave.And again hopelessness and the sense of doom .... All this went on for a very long time .... Gradually, I began to come back to reality ... .It was not a dream and I didn't want to sleep; it was simply a desire to lie calmly. I was thinking of my experience and gloomily analyzing it. I also thought about the questions I had been asked during the procedure .... In my opinion, I had heard everything, about alcohol, the attitude towards it, its consequences and about 'the finale' and my feelings ....My general condition: perfect physical state, strangely depressed psychological state (without any reason), a desire to somehow analyze my past life, some dull ache at the thought about past years, and some sharpened homesickness .... The attitude towards alcohol or anything similar: fear, a vague fear of everything that could disturb my distinct and clear consciousness and return it to something like what I had previously experienced. Be it some drink or injection or pills, it made no difference. If only the sober state were not disturbed, not even a little ....

In addition to the transpersonal experience, ketamine also often induces a psychodynamic experience, a form of life review related to the patient's history and maladjustive patterns, which are then presented in symbolic form in the patient's visionary experience. Because of these powerful mind-altering effects, ketamine belongs to the class of psychopharmacological compounds known as psychedelics. The majority of psychedelic compounds, however, are illegal to use in the United States for therapeutic applications. In contrast, ketamine is not on Schedule I and is readily available to physicians as a legal anesthetic under the U.S. Controlled Substances Act of 1970. It can also be lawfully administered "off-label" in psychiatric treatment as an adjunct to psychotherapy, when administered by a licensed physician.

HISTORY OF KPP

Exploration of the use of ketamine as a psychotherapeutic agent began during the late 1960s with the work of Lilly (1988), who conducted initial research with ketamine as an agent to induce nonordinary states of consciousness. In his research, Lilly administered ketamine both inside and outside of an isolation tank and determined the relationship between the dosage and the nature of the ketamine experience. He found that an intramuscular injection of up to 25mg of ketamine does not produce visions, doses above 30mg induce visual images with closed eyes, doses above 75mg cause patients to externalize visual experience and detach the mind from the physical body, doses above 150mg cause complete dissociation from the physical body and the subject becomes a KET AMINE PSYCHEDELIC PSYCHOTHERAPY 71 participant in an intense visual experience and doses above 300mg cause unconsciousness (Lilly 1988, pp. 168-75). Khorramzadeh and Lofty (1973) were the first to study the use ofketamine in psychiatry. They administered ketamine to 100 psychiatric patients with various psychiatric and psychosomatic diagnoses, including depression, anxiety, phobias, obsessive-compulsive neurosis, conversion reaction, hypochondriasis, hysteria, tension headaches, and ulcerative colitis. They reported that 91 of their patients were doing well after six months, and 88 remained well after one year. Complica- tions were minimal and included apprehension (two subjects), nausea (three subjects), and vomiting (two subjects). They concluded that ketamine's "abreactive (cathartic) effect correlated well with ketamine's mind-expanding effect." Khorramzadeh and Lofty (1976) also studied the correlation of the patient's personality with the types of ketamine-induced emergence phenomena. They used a Persian adaptation ofEPI (Eysenck's Personality Inventory) to evaluate the three dimensions of personality-Extraversion (E), Neuroticism (N), and Psychoticism (P)-in 606 patients who undertook ketamine anesthesia during surgery. They reported the following findings. Patients who scored high in E experienced pleasant dreams and some of them felt they were in heaven. Later questioning showed they were all devoted believers. Patients who scored high in N reported feeling dizzy because of an experience of rapid falls or circular movements. Patients who scored high in P reported loss of control over their limbs and a sensation of floating out of a body. In some, the reaction was such that the experience had to be ended with Perphenezine 5mg 1M. Patients who scored high for both Nand P had the combined experiences of groups Nand P, making them feel very apprehensive and frightened. Patients who scored high in both P and E stated that they had a good time and screamed or laughed because of the pleasant feeling. Patients who had high scores in Nand E reported they had a feeling of falling or spinning that was rather pleasant. Fontana (1974) used ketamine as an adjunct to anti-depressive psychotherapy in order to facilitate "a deep regression to prenatal level, experienced as disintegration and death, followed by a progression experienced as a rebirth." He reported that ketamine "allows the therapist not only to witness the dream but also to introduce himself into it and to correct, in situ, the primitive experience through the bi-personal relationship." He emphasized the advantages of ketamine, which made it possible "to reach such levels of regressions as had never been observed before" (p. 39). Roquet (1974) was the first clinician to employ KPP in a group setting. He combined psychoanalytic technique with the healing practices of Mexican Indian ceremonies and created a new approach to psychedelic psychotherapy that he called psychosynthesis, not to be confused with psychosynthesis as developed by Roberts Assagioli (1965). Roquet primarily treated neurotic patients, although he described some success with personality disorders and selected psychotic patients. His therapeutic program incorporated other psychedelic substances 72 TREA TTNGSUBSTANCE ABUSE and plants in addition to ketamine, such as LSD (lysergic acid diethylamide), peyote, psilocybin-containing mushrooms, morning glory seeds, and Datura ceratocaulum. Grof (1980) has developed the most comprehensive theory of psychedelic psychotherapy from the transpersonal perspective. He wrote that psychedelics facilitate therapeutic experiences of symbolic death and rebirth of the ego, allowing clients to work through deep traumatic fixations in their unconscious. Grof designed a specific psychedelic psychotherapeutic approach, which he applied successfully to more than 750 patients. Although Grof primarily used LSD in his work, he acknowledged that ketamine holds great promise because of its "affinity for positive dynamic systems." He reported that the psychoactive effect of ketamine is so powerful that "it catapults the patient beyond the point of impasse from the previous LSD session, and can make it possible for him or her to reach the better level of integration"(p. 214). Most current research in the United States employs a predominantly experimental perspective, where the psychedelic state induced by ketamine is often considered as a model of psychosis. The majority of the biochemical studies of ketamine have been carried out by Yale researcher John Krystal. Although most of KrystaJ' s research has concentrated on the effects of ketamine on perceptual and cognitive functioning (Krystal et al. 1994), his group of investigators also completed a clinical study documenting the antidepressant effects of ketamine (Berman et a1. 2000). No clinical research is currently underway in the United States into the usefulness ofketamine for the treatment of alcoholism and other drug addictions, although some U.S. researchers are investigating the use of ketamine for treatment of severe intractable pain (Carr et al. 2004). The treatment is used particularly for management of neuropathic pain disorder, ischaemic limb pain disorder, and refractory cancer pain. Another group of U.S. researchers has recently published the results of a randomized trial ofketamine for the treatment of mood disorder (Zarate et al. 2006). This study showed ketamine to be significantly effective for treatment-resistant major depression. Evgeny Krupitsky has conducted the most comprehensive and rigorous scientific clinical research on KPP to date. He began using ketamine as an agent for psychedelic psychotherapy in 1985 in the former Soviet Union. Since 1985, Krupitsky has used KPP without complications to treat more than 1,000 patients in his center. His early exploration of the use of ketamine as a psychotherapeutic agent employed, in part, an aversive conditioning model for the treatment of alcohol dependence. His later work included treatment of both alcohol and heroine dependence with KPP and gradually shifted to an existential model, as well as a transpersonal paradigm. Krupitsky's studies (Krupitsky et al. 1992; Krupitsky and Grinenko 1997) clearly demonstrated that KPP increases the rate of abstinence in patients with alcoholism. Of the subjects who received KPP, 69.8 percent were sober one year later, while only 24 percent in the control group remained abstinent during the KET AMINE PSYCHEDELIC PSYCHOTHERAPY 73

one-year follow-up period. In addition, Krupitsky's study (2002) with heroin addicts established that KPP increases the rate of abstinence in patients with heroin dependence. The study showed that the rate of abstinence in the KPP group at the end of the one-year follow-up period was five times higher (25 percent) than that ofthe control group (5 percent), while the corresponding rate ofre\apse was lower. The study also documented that KPP considerably reduced the craving for heroin. In addition, the study showed that ketamine psychotherapy produced no significant adverse reactions. The later study, which was the first double- blind clinical trial ofKPP conducted entirely within the evidence-based medical paradigm, clearly demonstrated the efficacy of psychedelic psychotherapy. Krupitsky (Krupitsky et al. 1992; Krupitsky and Grinenko 1997; Krupitsky et al. 2002) reported also that his patients, both alcoholics and heroin addicts, showed significant improvement after KPP. They became less anxious and depressed, more responsible and emotionally mature, with increased ego strength and positive changes in self-concept. The studies also showed that KPP brings about profound positive changes in life values and purposes and in attitudes to the different aspects of life and death, while accelerating psychospiritual development. Patients began to see other purposes, other values, other meaning and pleasures in their lives, grew more self-confident and balanced, more emotionally open and self-sufficient, and more responsible for their lives and the lives of their loved ones. Many of Krupitsky' s patients converted to a more spiritual approach to life through their transpersonal experiences, despite living in a country steeped in atheism for three generations. These encouraging clinical results occurred because of positive changes in the life values and purposes, relationships, and worldviews of these patients. They showed a transformation of emotional attitudes; a decrease in their level of inner discord, internal tension, discomfort, and emotional isolation; improved self-assessment; and a tendency to overcome the passive aspects of their personalities. These significant changes, along with a positive transformation of the patients' system of life values and changes in their world view, created a positive attitude toward a sober life and supported patients' ongoing stable sobriety.

RANGE OF THERAPEUTIC APPLICATIONS OF KPP

Previous studies of psychedelic psychotherapy (Leary et a1. 1964; Kurland et a1. 1971; Khorramzadeh and Lofty 1973, 1976; Roquet 1974; Grinspoon and Bakalar 1979; Grof 1980; Krupitsky et a1. 1992, 1997,2002; Strassman 1995; Jansen 1997, 200 \) suggest that the transpersonal experience may have beneficial effects in many ways, including:

• Contributing to the cathartic process; • Stabilizing positive psychological changes; 74 TREATINGSUBSTANCE ABUSE

• Enhancing personal growth and self-awareness; •Catalyzing insights into existential problems; • Increasing creative activities; •Broadening spiritual horizons; •Harmonizing relationships with the world and other people.

The breadth of potential psychological growth associated with psychedelic psychotherapy has led to the use of KPP for treating a variety of psychological problems. Khorramzadeh and Lofty (1973, 1976) successfully applied ketamine for treatment of both psychiatric illnesses (depression, anxiety, phobias, hypochondriasis, hysteria, obsessive-compulsive neurosis, and conversion reaction) and psychosomatic disorders (tension headaches and ulcerative colitis). They reported that 91 percent of their patients were doing well after six months, and 88 percent remained well after one year. Krupitsky et al. (1992) initially used ketamine as an alternative treatment for alcoholism only. They reported that KPP demonstrated a significant clinical effect when used in the treatment of alcohol dependence. Of 111 patients who received KPP in one study, 69.8 percent were sober one year later, while only 24 percent in the control group remained abstinent during the one-year follow-up period. Krupitsky concluded that KPP is a safe and effective alternative treatment for alcoholism. Krupitsky and Grinenko (1997) later demonstrated in their extensive clinical studies that KPP is highly effective in the treatment of alcoholism. Based on separate clinical observations, they also suggested that KPP might be helpful for the treatment of post-traumatic stress disorder, reactive depression, neurotic disorders, avoidant personality disorders, phobic neurosis, obsessive-compulsive neurosis, and histrionic personality disorder. Later Krupitsky and his team (Krupitsky et al. 2002) examined the effectiveness of KPP for heroin dependence in a double-blind, randomized clinical trial. The team found that the rate of abstinence in the ketamine group was significantly higher than that in the control group, while the corresponding rate of relapse was lower. This study documented that KPP significantly reduced the craving for heroin, considerably decreased the levels of anxiety and depression, markedly increased the level of spiritual development, and to a great extent, enhanced the understanding of the meaning and purpose of life. The study also demonstrated that KPP produced no significant adverse reactions, and no subject participating in the study became addicted to ketamine. This may be the result of the special psychotherapeutic set and setting or the inclusion criteria, since subjects with episodes of major psychiatric disorders in the past and poly-drug dependency were not included in the study. The results may also be related to the mechanism underlying ketamine action, the blockade of the N-methyl-D-aspartic acid receptor, which is different from that of other psychedelics, which are primarily serotonin partial agonists. KETAMINE PSYCHEDELIC PSYCHOTHERAPY 75

The present body of research clearly documents that KPP is an effective tool in the treatment of addiction. Although studies of KPP to date ha ve concentrated on the treatment of alcoholism and opioid dependency, the results of research may be extrapolated to the treatment of other addictions, as it is evident that a ketarnine-induced transpersonal experience is auspicious for a sober life in general. In addition, previous empirical studies and Krupitsky's recent research have further demonstrated the effectiveness of KPP in the treatment of neurotic disorders, psychosomatic illnesses, and personality disorders.

BEST USES AND PRACTICES

The technique of KPP has evolved as a specialized procedure with the goal of inducing an ego-dissolving transpersonal peak experience. The method generally includes from one to three sessions with ketamine and depends on set or expectations, setting or environment, and the dosage of the drug. It is very important to emphasize that ketamine by itself is not the healing agent but is an adjunct to the psychotherapeutic process involved in the treatment of underlying bio-psycho-socio-spiritual problems. KPP comprises three main stages: preparation, administration, and integration. In the preparation stage, preliminary psychotherapy is carried out with patients, who are told that the psychedelic session may induce important insights concerning their personal problems, their systems of values, their notions of self and the world around them, and the meaning of their lives. Patients are educated that all of these insights may lead to positive changes in their personalities, which will be important for healing their underlying problems and shifting to a sober lifestyle. At least 5 to 10 hours of psychotherapy is provided before the ketamine session in order to establish the psychospiritual goal for the transpersonal experience and prepare the subject for the session. This information is not presented in the form of a didactic monologue from the psychotherapist. The abstract "psychotherapeutic myth" is not simply explained to the patient; it is discussed with him or her and embroidered with specific concrete content during an ongoing dialogue. The therapist pays close attention to issues such as the patient's personal motives for treatment, goals for a sober life, and ideas concerning the cause of the disease and its consequences. The patient and the therapist together form an individually tailored "psychotherapeutic myth" during this dialogue that creates an atmosphere of confidence and mutual understanding during the first stage of KPP. This then becomes the most important therapeutic factor responsible for the psychological content of the second stage ofKPP. The second stage of KPP is the induction of the transpersonal experience through the administration of ketamine. Breakfast is omitted on the morning of ketamine administration, and all participants refrain from food and drink for at least eight hours prior to this experience. Patients are told that they will enter 76 TREATING SUBSTANCE ABUSE some unusual states of consciousness and are instructed to surrender fully to the experience. After the patient lies down in a comfortable supine position with eyeshades, ketamine is injected intramuscularly, in doses from 2.0 to 2.5mg/kg. The intramuscular route is preferred because the effect is more gradual and the psychedelic experience lasts longer. With an intravenous psychedelic dose (from 0.7 to 1.0mg/kg), the effect lasts only about 15 to 20 minutes, but with an intramuscular injection, it lasts from 45 minutes to an hour. With a background of specially chosen music-generally, free-floating nonassociative classical or New Age music-the patient typically has an ego- dissolving transpersonal peak experience. After 45 minutes to an hour, the patient slowly comes back from the experience. During the recovery period, which takes from one to two hours, the patient begins to feel ordinary reality returning. At this point in the session, the patient usually begins to describe the experience, and some discussion and interpretation is begun with the psychotherapist. After the session, the patient goes to rest. The patient is asked to write down a detailed self-report of the transpersonal ketamine experience that evening. The third stage is integration of the transpersonal experience, which is carried out after the ketamine session. It is generally done in a group psychotherapy format, because the dynamic of the shared group experience is more powerful and therapeutic than individual therapy alone. Three to five hours of psychotherapy is provided after the ketamine session to help subjects interpret and integrate their experiences during the session into everyday life. With the aid of the psychotherapist during the integration phase of treatment, the patients discuss and interpret the personal significance of the symbolic content of their ketamine-induced transpersonal experiences. This discussion is directed toward helping the patients make a correlation between their psychedelic experience and their intra- and interpersonal problems. The therapist assists the patients in the psychological integration of the spiritual transformation that can result from the direct transpersonal experience. This uniquely profound and powerful experience often helps patients to generate fresh insights that enable them to integrate new, often unexpected meanings, values, and attitudes about the self and the world. Treatment-resistant patients may require a second or even a third ketamine session. This approach springs from observing a specific "psychedelic afterglow" that many of the subjects reported after undergoing psychedelic psychotherapy (Grinspoon and Bakalar 1979). This afterglow included positive psychological changes induced by the psychedelic session that usually lasted up to several weeks. One of the insights gained from previous research with psychedelics concerns the transient psychotherapeutic and psychological effects of psychedelic psychotherapy. The effects of psychedelic psychotherapy are often very pro- nounced within several weeks after a treatment session, but afterward these effects may start declining (Halpern 1996). Thus, repeated KPP sessions might have a cumulative effect that would generate longer-lasting positive KETAM1NE PSYCHEDELIC PSYCHOTHERAPY 77

psychological changes, thereby improving treatment outcomes. The data from the most recent study by Krupitsky's team (2006) provide some evidence that three repeated KPP sessions work better and provide a higher rate of abstinence in heroin addicts than one KPP session, suggesting that increasing the number of KPP sessions increases the efficacy of treatment.

POSSIBLE MECHANISMS OF EFFECTIVENESS

The acute psychological effects of ketamine are psychedelic in nature. One study (Krupitsky et al. 2002) demonstrates that ketamine-enhanced psychotherapy is more effective when a high psychedelic dose of ketamine is administered (2.0 to 2.Smg/kg 1M) than when a low sub-psychedelic dose is administered (0.2mg/kg 1M). Although a sub-psychedelic dose of ketamine induces some pharmacological effects, it does not induce a full psychedelic peak experience and, therefore, does not create a nonordinary state of consciousness. Quantitative assessment of ketamine-induced effects in the high- dose group using the HRS(Hallucinogen Rating Scale developed by Strassman et al. (1994) was similar to the assessment of effects induced by a dose of N,N-dimethyltryptamine (the tryptamine hallucinogen, DMT), described by experienced psychedelic users as fully psychedelic (Strassman 1996). All but one HRS subscale scores differed significantly between the high-dose and the low-dose groups. Subjects in the high-dose group had a typical psychedelic peak experience, while patients in the low-dose group experienced something that functions as ketamine-facilitated guided imagery (Leuner 1977). High- dose KPP produced a significantly greater rate of abstinence in heroin addicts within the first 24 months of follow-up than did low-dose KPP.High-dose KPP brought about a greater and longer-lasting reduction in craving for heroin, as well as greater positive change in nonverbal unconscious emotional attitudes. A ketamine-induced psychedelic experience significantly differs from those of serotonergic hallucinogens, such as LSD, psilocybin, and DMT. It is, to some extent, similar to the NDE(near-death experience) (Jansen 1997,2001). Typical characteristics of an NDE include:

• A sense that one is truly dead; • A perception of separation from the body, or out-of-body experience; • A sense that what is experienced is real; Ineffability, or a sense that the experience is beyond words and cannot be described using language; •Transcendence of time and space.

The following three case studies demonstrate the nature of the ketamine- induced NDE that is described by these patients:

---~~.-- ... 78 TREATrNG SUBSTANCE ABUSE

Patient V.Z.: I lost myself. I felt bewilderment because I lost myself, my body. Then it was death. Death, a calm flight downward through dense gray-and-white clouds. And suddenly rebirth. At somebody 's command I saw a series ofterrifying pictures on a red background. They moved horizontally, picture by picture, independently of each other. They depicted the sad scenes of the alcoholic life. Filth, broken bottles, corpses, horrible faces, drunken grimaces. It was absolutely clear that this would be my future, the future of people like me (if we did not give up drinking). The desire to tell everybody as soon as possible where this would lead us was also horrible to feel. Fast movement by some strange vehicle, a kind oftrain. And here the disgusting smell of alcohol, then the oath of sobriety. Dissatisfaction. As if everything should be done some other way. People must know about my oath and hear it. ...

Patient P.K.: I found myself inside a gigantic tunnel whose mouth reached a terrifying height, and there, on the top, was nothing .... A red capsule spiraled rapidly to the top along the surface of the tunnel. And I was in this capsule-or even this capsule was myself and it was me who was rushing towards nothing. But at the same time, I regarded myself in a detached spirit, as if I were split apart. ... Abruptly, I found myself on the top of the tunnel. What I saw made me shudder with horror. A horrible, dark and cold abyss gaped in front of me. It was as if I were in an open space, infinite and impossible to perceive. Each cell of my body felt the horror of this abyss. One more turn and I would find myself in this obscu- rity and drop and drop endlessly Even after the procedure, when I remem- bered this, it made me feel uneasy But there was no other turn. Everything got mixed up, went round, and this whirl took me upward .... I felt that I was rushing at a high speed along some glass tunnel; through the glass I could see somebody's face and somebody asked me if I would drink. 1 answered that no, I wouldn't .... 1 came to understand that this gaping abyss where 1 would be completely alone would be my fate, if 1 would not give up drinking.

Patient P.F.: In my whole body music starts playing in synchrony with the switched-on tape-recorder. I've got an irresistible feeling of being carried away. I try to resist it with all my forces, but can't. It's as if a train disappears in the tunnel and you are flying after it into this black abyss and can't resist it. The music is deafening; your whole body obeys it. It is as if your body is pulsating in unison with the music. And you are flying in pitch-darkness, and at the same time you are hearing the doctor's voice telling you about aversion to alcohol, about the sober life and so on. Then, a flash of light. You are always moving and feel as if you are a ball among other balls rolling along a corridor lined with similar balls. Always dead ends, turns, flights and drops; turning into a cube with smoothed edges. The illu- mination and color of the corridor where you are rolling also changes. KETAMTNE PSYCHEDELIC PSYCHOTHERAPY 79

Or suddenly everything is ruined by a wave, and you are going with the wave along the corridor. Then, everything bumps into something. The splash reaches the sky and you become a brilliant white point flying in space.Then you burst into thousands of splashes, and again turns, nooks, flights and drops, but always in a rush and always ahead, ahead ....Abruptly, everything starts going round, becomes a small point. This point turns into a gold hair and the whole universe turns out to be hanging by it. You see it clearly. You are feeling the responsibility for everything alive and this depresses you. Then everything turns into silvery stars forming a dome, and you are one of the stars. Then the whole dome collap- ses and turns into one dot. A gold splash appears against the blue background. It turns into a flower. The flower opens and there, in the flower, I see my son, and somebody's voice is saying: "That is most important."

Approximately 70 percent ofNDEs are accompanied by feelings of calm and peace, and about 30 percent of NDEs are very frightening. Past memories are often organized into a life review. Transcendent mystical states are common, with visions that include surreal landscapes; meaningful figures, such as parents, teachers, partners, or friends, who may be already dead or still alive at the time; and archetypal images, such as angels, Bodhisattvas, Christ, or any other pres- ence in the pantheon of gods and goddesses. The experience of God is often reported as an ocean of luminescent white light. The intramuscular administration of 150 to 200mg ofketamine can repro- duce all of the features commonly associated with NDEs (Lilly 1988; Jansen 1997, 2001). A previous study indicates that NDEs frequently trigger transfonna- tive and healing changes (Ring 1984). Analogous to the spontaneous NDE, a ketamine-induced DE-like psychedelic experience may facilitate stable recovery and induce changes in spiritual development and worldview (Krupitsky and Grinenko 1997). Scientific publications (Grof 1980; Kurland et al. 1971;Whitfield 1984; Corrington 1989; Halpern 1996; Krupitsky and Grinenko 1997) suggest that transpersonal spiritual experience is an important factor in a recovery from addiction to various substances. For example, Alcoholic Anonymous' cofounder, Bill Wilson, recovered from Alcoholism after he had a profound spontaneous transpersonal experience in 1934. After that experience, he said he never again doubted the existence of God and never took another drink (Alcoholic Anonymous World Services 1984, pp. 120-21). This is a well-known fact, and subsequently, Alcoholic Anonymous and various other substance/habit Twelve-Step programs have adapted a distinctly spiritual orientation (Whitfield 1984;Corrington 1989). It is a lesser-known fact, however, that in 1956 Bill Wilson took a psychedelic compound (LSD) under the guidance of Sidney Cohen, a psychiatrist at the Los Angeles Veterans Administration Hospital. He had an intense experience that was "totally spiritual," similar to his initial spiritual experience. Wilson felt that the second spiritual experience helped him eliminate "many barriers erected by the self, or ego" and thought he 80 TREATING SUBSTANCE ABUSE

"might have found something that could make a big difference to the lives of many who still suffered" from alcoholism (Alcoholic Anonymous World Services 1984, pp. 368-71). A therapy that enhances the likelihood ofa spiritual experience, therefore, may have utility in the treatment of substance abuse. Ketamine-enhanced psychotherapy may present one method of eliciting spiritual experiences in subjects with chemical dependencies and thus help support abstinence. Previous studies (Krupitsky and Grinenko 1997; Krupitsky et a1. 2002) have revealed that patients who were treated with KPP reported they were better able to understand the meaning of their lives, their life purposes, and perspective on new directions in life.All patients demonstrated positive changes in life values, reflecting an increased understanding and importance of life values other than "getting high." Relative to Frankl's (1978) approach, which consid- ers alcoholism and other addictions as an "existential neurosis" resulting from loss of meaning of life (existential void),KPP may help fill this void to a major extent. Therefore, it is beneficial to combine KPP with existential psychotherapy, which focuses on universal concerns that are deeply rooted in the very nature of human existence. Studies of the underlying psychological mechanisms of KPP (Krupitsky and Grinenko 1997; Krupitsky et a1. 2002) have indicated that KPP induces a harmonization of the MMPI (Minnesota Multiphasic Personality Inventory) personality profile, showing that patients became more confident, more optimis- tic about their possibilities and their futures, less anxious, less depressed and neurotic, and more emotionally open after treatment.Other psychological measures in these studies have demonstrated positive transformation of the nonverbal, mostly unconscious, self-concept and emotional attitudes toward various aspects of self and other people, positive changes in life values and purposes, important insights into the meaning of life, and an increase in the level of spiritual development.These important psychological changes were shown to favor a sober lifestyle. The data from biochemical investigations (Krupitsky et a1. 1990) showed that pharmacological action of KPP affects both monoaminergic and opioider- gic neurotransmitter metabolism, i.e., those neurochemical brain systems involved in the development (pathogenesis) of alcohol dependence.It is possible that these processes underlie, to a certain extent, the efficiency of this method. The data from EEG computer-assisted analysis (Krupitsky and Grinenko 1997) demonstrated that ketamine increases delta-activity (by 1.5-2 times) and particularly theta-activity (by 3-4 times) in all regions of the brain cortex. This is evidence of limbic system activation during ketamine session, as well as evidence of the reinforcement of the limbic-cortex interaction. This can also be considered as indirect evidence of the strengthening of the interactions between the conscious and subconscious levels of the mind during KPT. KET AMINE PSYCHEDELIC PSYCHOTHERAPY 81

POTENTIAL FOR KET AMINE MISUSE

Ketamine belongs to the same group of chemicals as PCP (Semyl, phencyclidine). This group of chemical compounds is called arylcyclohexylamines and is classified as hallucinogens, or psychedelics. Ketamine is a controlled substance and is listed on Schedule III of the Controlled Substances Act of 1970. Medical evidence regarding the issue of drug abuse and dependence suggests that ketamine abuse potential is equi valent to that of PCP and other hallucinogenic substances (Siegal 1978). PCP and other hallucinogenic compounds do not meet the criteria for chemical dependence, since they do not cause tolerance and withdrawal symptoms. However, cravings have been reported by individuals with a history of heavy use of psychedelic drugs. In addition, ketamine can have effects on mood (feelings), cognition (thinking), and perception (imagery) that may make some people want to use it repeatedly. Therefore, ketamine should never be used except under the direct supervision of a licensed physician.

FUTURE DIRECTIONS FOR RESEARCH

Research conducted by a Soviet scientist supports the conclusion that KPP is highly effective for the treatment of alcoholism and opioid dependency (Krupitsky et al. 1992; Krupitsky and Grinenko 1997; Krupitsky et al. 2002). This research was confirmed through clinical observation and was recently reported by an American researcher (Kolp et al. 2006). Kolp has recently designed two double-blind, randomized clinical trials of the efficacy ofKPP as an enhancement to standard treatment of alcohol dependence (study #1) and opioid dependence (study #2). In both studies, following patient selection and consent procedures, the patients will receive two sessions with ketamine or placebo on the 8th and 15th days of standard treatment in a three-week residential program. Long-term outcome will be measured every six months for two years following discharge. The funding to carry out these studies is currently being sought through a clinical grant research from the NIAAA and the NIDA. Because KPP is very effective for the treatment of dependency on two CNS (central nervous system) depressants, ethyl alcohol and opiates, it is possible to hypothesize that KPP is also equally effective for the treatment of dependencies to other CNS depressants, such as benzodiazepines and barbiturates. Other plans include conducting two clinical trials of the efficacy ofKPP as an enhancement to standard treatment for dependency on benzodiazepines and barbiturates. In addition, preliminary studies (Krupitsky and Grinenko 1997) have demonstrated that KPP is effective for the treatment of dependency on ephedrine, a CNS stimulant. These data suggest that KPP may be effective for treatment of dependencies on other psychostimulants, such as nicotine, caffeine, cocaine, and amphetamines.Long-term plans are in place to conduct clinical trials of the 82 TREATINGSUBSTANCE ABUSE efficacy of KPP as an enhancement to standard treatment of tobacco dependence and cocaine dependence. The study of the use of ketamine in psychiatry (Khorramzadeh and Lofty 1973) demonstrated a significant improvement in patients with different psychiatric disorders and psychosomatic illnesses. Further research is indicated to evaluate the effectiveness of KPP in the treatment of patients with various psychiatric diagnoses, specifically mood disorders, such as reactive depression, seasonal depression, and cychlothymia; anxiety disorders, such as generalized anxiety disorder, phobias, obsessive-compulsive disorder, and hypochondriasis; and eating disorders, such as binge eating disorder and food addiction. Further research is also indicated in patients with various psychosomatic diagnoses, especially tension headaches, migraine headaches, pain disorder, irritable bowel syndrome, fibromyalgia, and chronic fatigue syndrome. Khorramzadeh and Lofty (1976) established a correlation between the patient's personality and the type ofketamine-induced psychedelic experience. These results were confirmed by Krupitsky and Grinenko (1997). More research is needed to further explore this connection between the patient's personality profile and the nature of the ketam ine transpersona1 experience, as well as the relationship between both phenomena and the subsequent response of patients to treatment with KPP. Another potential area of research is to explore the similarities between a ketamine-induced transpersonal experience and an NDE, as previously reported by Jansen (1997, 2001). A planned future study will involve the administration of a psychedelic dose of ketamine to persons who have had an NDE to collect psychological measures for comparing the two experiences.

CONCLUSION

Ketamine is a legal aesthetic under the U.S. Controlled Substances Act of 1970 and can be lawfully administered "off-label" in psychiatric treatment as an adjunct to psychotherapy, when administered by a licensed physician. In a sub-anestethic dose (about one-sixth to one-tenth of that typically used for general anesthesia), ketamine acts as a psychedelic compound and induces a profound trans personal experience lasting from 45 minutes to one hour. Unlike other psychedelics that are illegal to use in the United States, ketamine is readily available to physicians for psychotherapeutic applications. In addition, ketamine has other advantages over the majority of psychedelic compounds because of its large margin of safety, rapid onset, and short duration of action. The body of scientific research clearly documents that KPP is an effective tool in the treatment of chemical dependencies on CNS depressants (alcohol and opioids) and, to some extent, CNS stimulants (ephedrine). Additional data also show that ketamine can be successfully applied for treatment of psychiatric illnesses (depression, post-traumatic stress disorder, phobias, and KETAM]]\,'E PSYCHEDELIC PSYCHOTHERAPY 83 obsessive-compulsive disorder), selected personality disorders (avoidant personality disorders and histrionic personality disorder), and some psychosomatic illnesses (tension headaches and ulcerative colitis). The studies demonstrated that the majority of patients showed significant improvement after KPP. They became less anxious and depressed, more responsible and emotionally mature, grew more self-confident and balanced, and more emotionally open and self-sufficient, with increased ego strength and positive changes in self-concept. Empirical observation and clinical research have shown that a ketamine- induced transpersonal experience decreases the level of inner discord and internal tension, reduces discomfort and emotional isolation, improves self-esteem, and causes a positive transformation of emotional attitudes. In addition to these emotional benefits, KPP patients experienced significant existential and spiritual growth, including improved attitudes to various aspects of life and death, profound positive changes in their worldview, and accelerated psychospiritual development. They began to see other life values and purposes and other meaning and pleasures in their lives, and they became more responsible for their lives and the lives of their loved ones. These transformations reinforced patients' positive attitudes toward a sober and healthy lifestyle and supported their ongoing stable recovery from chemical dependency. The existing body of research indicates that KPP is a promising psychotherapeutic technique for effective treatment of substance dependencies, psychological disorders, and psychosomatic illnesses. Continued scientific research of KPP in well-controlled studies is highly indicated because of its proven therapeutic effectiveness and biological safety.

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