Ketamine Psychedelic Therapy in the Treatment of Heroin Addiction
Evgeny Krupitsky, M.D., Ph.D. and Andrei Burakov, M.D., Ph.D.
Research Laboratory, Leningrad Regional Center for Alcoholism and Drug Addiction Therapy.
Novo-Deviatkino 19/1, Leningrad Region 188661, RUSSIA
  1. To conduct a double-blind controlled study of the clinical efficacy of ketamine-assisted psychedelic psychotherapy for heroin addiction. We seek to determine whether ketamine psychedelic therapy (KPT) will improve the efficacy of conventional methods of treatment of heroin addiction as reflected in objective measures of therapeutic outcome. This outcome would be demonstrated by statistically greater and/or more sustained clinical and psychological improvements in the heroin addicts undergoing KPT.
  2. To study underlying psychological mechanisms of KPT of heroin addiction. We seek to determine which kinds of psychological transformations induced by KPT help heroin addicts to stay abstinent from heroin.

In the 1950s and 1960s, many studies suggested that psychedelic psychotherapy might be an efficient treatment for the addiction (Grinspoon and Bakalar, 1979). Unfortunately, differing methodologies made it difficult to generalize across studies. The requisite development of appropriate sophistication of these studies was not possible after psychedelics were scheduled in 1970 and their use was strictly limited. Fortuitously, at about this time, ketamine and ketamine-like anaesthetic agents were observed to elicit "psychedelic" emergent phenomena in patients (Loh et al., 1972; Khorramzadeh and Lofty, 1976). This property was explored in our use of KPT for alcohol dependency, and the method appeared to be very effective (Krupitsky, 1992, 1995; Krupitsky and Grinenko, 1992, 1996; Krupitsky et al., 1992, 1996). Ketamine has some advantages over other psychedelics as an adjunct to psychotherapy. It is safe and short-acting (the psychoactive effects last about an hour), it is not scheduled like other psychedelics, and in small subanaesthetic doses it can induce profound psychedelic experiences. As conventional methods of therapy for heroin addiction have low rates of efficacy, research investigating new, potentially more effective approaches, such as KPT, are needed.


I. Design

All patients will be randomly assigned to one of two groups. The experimental group will receive standardized psychotherapy, described later, with the addition of a "psychedelic" dose of ketamine (2.5 mg/kg i.m.). The control group will receive the same standardized psychotherapy with the addition of a very low non-psychedelic (non-hallucinogenic) dose of ketamine (0.25 mg/kg i.m.) which induces some pharmacological effects but without the peak psychedelic experience. Both the psychotherapist and the patient will be blind to the dose of ketamine administered. All patients will be treated alike and will be given the same preparation and follow-up. The KPT sessions, regardless of dosage, will be given under identical circumstances. Psychological and clinical evaluations prior to treatment and during the follow-up period will be done by a clinician evaluator other than the psychotherapist providing KPT.

II. Patients

Sixty heroin addicts will be screened, evaluated and randomized into the study. Patients will be recruited from the in-patient department of the Leningrad Regional Center for Alcoholism and Drug Addiction Therapy after they have completed the standard regimen of detoxification. Informed consent will be obtained from all patients prior to acceptance into the study. All patients will be accepted in the study as in-patients and will be discharged from the hospital one week after they have completed this treatment.

III. Psychotherapist

Psychotherapy will be provided by a psychotherapist (MD) who is specially trained in KPT. Each patient will undergo only one KPT session.

IV. Patient Selection

   a) Inclusion criteria

  • ICD-10 criteria for heroin addiction;
  • age between 21 and 60;
  • at least high school education;

   b) Exclusion criteria

  • ICD-10 criteria for organic mental disorders, any kind of personality disorders, schizophrenic disorders, paranoid disorders, major affective disorders, and seizure disorders;
  • ICD-10 criteria for alcoholism and polydrug dependency.
  • Advanced cardiovascular, renal, and hepatic deseases;
  • Pregnancy;
  • Family history of psychiatric disorders listed above.

V. Screening Evaluation

  • Formal psychiatric examination
  • Standard medical examination, including blood chemistry panel (including hepatic functions), urine analysis, HIV-test, and EKG.
  • Review of previous medical and psychiatric records.

VI. Battery of Assessment Instruments

In choosing the battery of assessment instruments, care was taken to include those instruments which we successfully used in our previous studies of KPT of alcoholism in order to provide comparability with those studies. An effort was also made to provide a mix of instruments widely used in psychotherapy outcome research. In addition, due to the specific nature of psychedelic therapy, instruments were favored that might indicate changes in the areas of personality, life values, purpose, spiritual development and unconscious emotional attitudes.

Psychiatric Symptoms and Psychopathology:

  1. ICD-10 Structured clinical interview for psychiatric disorders (PSCI).
  2. Zung self-rating depression scale (ZDS) (Zung, 1965).
  3. Spielberger self-rating state-trait anxiety scale (SAS).
  4. Visual analog scale of craving (VASC)--100 mm line marked by subjects in proportion to the intensity of craving experienced while completing the scale.
  5. Addiction severity index (ASI) (McLellan et al., 1980)--clinician-administered instrument about problems in six areas: Drug use, medical, psychological, legal, social and occupational.

Psychological Assessments:

  1. Minnesota Multiphasic Personality Inventory (MMPI) (Dahlstrom et al, 1972).
  2. Locus of Control Scale (LCS) developed by Rotter (Phares, 1976) to assess the ability to control and manage different situations.
  3. Color Test of Attitudes (CTA) (Etkind, 1980)--to assess unconscious emotional attitudes.
  4. Questionaire of Terminal Life Values (QTLV) based on the Rokeach approach to human values and beliefs (Rokeach, 1973).
  5. Purpose-in-Life Test (PLT) (Crumbaugh, 1968) based on the Frankl (1978) concept of man's aspiration for the meaning of life.
  6. Spirituality Changes Scale (SCS) based on the combination of the Spirituality Self- Assessment Scale developed by Whitfield (1984), who studied the importance of spirituality in the Alcoholics Anonymous therapeutic program, and the Life Changes Inventory developed by Ring (1984) to estimate psychological changes produced by near- death experiences. SCS has been shown to be sensitive to the changes of spiritual development in our studies of KPT of alcoholism and in the studies of the effect of meditation on spiritual development (Krupitsky et al., 1996).
  7. Physical Health - Activity - Mood Scale (SFAM)--special 24-item visual analog scale. We will use specially adapted Russian versions of the international scales and questionnaires mentioned above.

VII. Treatment Assessment, Outcome and Follow-Up

Assessment Schedule:

  • PSCI and ASI will be administered only pre-therapy (baseline).
  • ZDS, SAS, VASC, MMPI, LCS, CTA, QTLV, PLT, and SFAM will be administered pre- therapy (baseline) and post-therapy (two to four days after the ketamine session) as a comprehensive test battery sensitive to the changes over the course of this study.
  • SCS will be administered only post-therapy two to four days after the ketamine session to assess spirituality changes in the patients of both the experimental and control groups. Full medical assessment including all laboratory tests will be repeated at the completion of treatment within one week of discharge.
  • All patients will also be asked to write a detailed self-report about their experiences during the ketamine session. This self-report will be evaluated by blind experts using standardized criteria to determine the presence or absence of a peak experience during the ketamine session.

Full medical assessment including all laboratory tests will be repeated at the completion of treatment within one week of discharge.

Urine drug screens will be conducted at the 3, 6, 12, 18 and 24 month time points.

Follow-Up Data:

Follow-up data will be collected by psychiatrists who will be blind to the kind of therapy (low or high dose of ketamine). Follow-up data will include:

  • Information from the patient about his/her drug use during the follow-up period.
  • Examination of the patient's veins for traces of injection.
  • Information from relatives and/or colleagues about the patient's drug use.
  • Urinalysis tests will be administered to patients of the experimental and control groups at months 3, 6, 12, 18 and 24 to confirm they are staying drug-free. In addition, urinalysis tests will be administered in between scheduled tests in cases where the information from relatives and/or colleagues about the patient's drug use suggests that the patient may have relapsed.
  • Urine drug screen, ZDS, SAS, VASC, and SFAM data at 3, 6, 12, 18 and 24 month time points.

VIII. Treatment Procedure

There will be up to 10 hours of psychotherapy provided before the ketamine session to prepare patients for the session. There will be up to 5 hours of psychotherapy provided after the ketamine session to help patients to interpret and integrate their experience during the session. An anesthesiologist will be present throughout the ketamine session to prevent any complications. The length of the ketamine session will be about 1.5 - 2 hours. Each patient will undergo only one KPT session. The patient will be instructed to recline on a couch with eyeshades. Pre-selected standardized stereophonic music will be used throughout the ketamine session. A psychotherapist will provide emotional support for the patient and carry out psychotherapy during the ketamine session. Psychotherapy will be existentially-oriented, but will also take into account the patient's individuality and personality problems. Description of the psychotherapy There are three main stages in our method of KPT (Krupitsky, 1992). During the ketamine sessions, patients often experience the separation of consciousness from the body and the dissolving of the ego, so it is very important to prepare them carefully for such an unusual experience.

First Stage:

The first stage is preparation. In this stage, preliminary psychotherapy is carried out with the patient. During these psychotherapeutic sessions it is explained to the patient that relief of their dependence on heroin will be induced in a special state of consciousness in which they will have a deep experience that will help them to realize the negative effects of heroin abuse, and the positive aspects of life without drugs. We explain that the psychedelic session may induce important insights concerning their personal problems, their system of values, notions of self and the world around them and the meaning of their lives. All of these insights may entail positive changes in their personality, which will be important for their shift to a new lifestyle without heroin. This information is not presented to the patient in the form of a didactic monologue from a psychotherapist. The abstract "psychotherapeutic myth" is not simply explained; it is discussed with the patient and embroidered with specific concrete content during a dialogue. The therapist pays close attention to the patient's personal motives for treatment, goals for a new life without drugs, ideas about the causes of the disease, its consequences, and so on. An individually-tailored "psychotherapeutic myth" is formed during this dialogue. It becomes the most important therapeutic factor responsible for the psychological content of the second stage of KPT. It is also very important to create a specific atmosphere of confidence and mutual understanding between the psychotherapist and the patient during the first stage of KPT.

Second Stage:

The second stage is the ketamine session itself. The second stage is conducted by two physicians, a psychotherapist and an anesthesiologist, because some complications and side-effects such as increased blood pressure, convulsions and shallowness of breath are possible, though exceedingly rare. With a background of special music (generally New Age composers such as Kitaro and Jean Michel Jarre), the patient having a KPT session is exposed to psychotherapeutic influences. The content of these influences is based on the concrete data of the patient's case history and is directed toward the resolution of the patient's personality problems and toward the formation of a stable orientation towards a life without drugs. We try to help our patients create new meaning and purpose in their lives during this session. The specific character of our KPT method allows us to carry out a special psychotherapeutic dialogue with the patient undergoing the psychedelic experience. We emphasize the positive values and meaning of life without drugs and the negative aspects of drug abuse during this dialogue, which has a specific personal orientation for each patient. We carefully direct the patient's psychedelic experience by verbal influences and by manipulating the musical background with the aim of promoting the symbolic resolution of personality conflicts and cathartic peak experiences. After the session, the patient rests for the remainder of the day. We ask them to write down a detailed self-report of their experience that evening.

Third Stage:

In the third stage, up to five hours of psychotherapy are carried out in the days after the KPT session. During these sessions, the patient discusses and interprets the personal significance of the symbolic content of his or her experience with the psychotherapist. This discussion is directed toward helping the patient make a correlation between his or her psychedelic experience and intra- and interpersonal problems (primarily those connected to drug abuse). this post-session psychotherapy helps to solidify the patient's desire for a life without drugs. We also try to assist patients to integrate the insights from the psychedelic session into their everyday lives. The uniquely profound and powerful psychedelic experience often helps them to generate new insights that enable them to integrate new, often unexpected meanings, values and attitudes about themselves and the world.

IX. Data Management and Statistical Analysis

All patient-related information will be filed under a study code number for purposes of confidentiality and to maintain the "blind" study design. Only one investigator will have access to the code manual, which will be kept in a secure and locked place. Routine statistical analysis will be performed to assess treatment effects and outcome both in the experimental and control group, and also statistical significance of differences between the experimental and control group. We will also look for correlations between the changes in the assessment instruments battery caused by KPT, content of KPT experiences (presence or absence of peak experience) and follow-up data.

X. Possible Project Duration

2.5 - 3 years.