Ketamine psychotherapy for heroin addiction: immediate effects and two-year follow-up

This randomized double-blind clinical trial (2002, n=70) found that existential psychotherapy in combination with psychedelic doses of intramuscular (im) ketamine (140mg/70kg) achieved larger results in the treatment of heroin addiction than sub-hallucinogenic doses (14mg/70kg).

Abstract

“Seventy detoxified heroin-addicted patients were randomly assigned to one of two groups receiving ketamine psychotherapy (KPT) involving two different doses of ketamine. The patients of the experimental group received existentially oriented psychotherapy in combination with a hallucinogenic (“psychedelic”) dose of ketamine (2.0 mg/kg im). The patients of the control group received the same psychotherapy combined with a low, non-hallucinogenic (non-psychedelic), dose of ketamine (0.2 mg/kg im). Both the psychotherapist and patient were blind to the dose of ketamine. The therapy included preparation for the ketamine session, the ketamine session itself, and the post session psychotherapy aimed to help patients to integrate insights from their ketamine session into everyday life. The results of this double blind randomized clinical trial of KPT for heroin addiction showed that high dose (2.0 mg/kg) KPT elicits a full psychedelic experience in heroin addicts as assessed quantitatively by the Hallucinogen Rating Scale. On the other hand, low dose KPT (0.2 mg/kg) elicits “sub-psychedelic” experiences and functions as ketamine-facilitated guided imagery. High dose KPT produced a significantly greater rate of abstinence in heroin addicts within the first two years of follow-up, a greater and longer-lasting reduction in craving for heroin, as well as greater positive change in nonverbal unconscious emotional attitudes than did low dose KPT.”

Authors: Evgeny Krupitsky, Andrey Burakov, Tatyana Romanova, Igor Dunaevsky, Rick Strassman & Alexander Grinenko

Summary

Abstract

Seventy heroin-addicted patients were randomly assigned to one of two groups receiving ketamine psychotherapy. The results showed that high dose ketamine produced a greater rate of abstinence, a greater and longer lasting reduction in craving for heroin, and greater positive change in nonverbal unconscious emotional attitudes.

1. Introduction

Psychedelic psychotherapy is a promising approach to the treatment of addiction, and ketamine is a useful drug in this regard. However, not all studies demonstrated positive outcomes, and different methodologies make it difficult to generalize results across studies.

Ketamine is a safe and short acting psychedelic that has been shown to be an effective treatment for alcoholism. It may possess similar anti-craving properties as acomprosate and ibogaine.

Treatments for addictions have included therapy and counseling, Alcoholics Anonymous, Narcotics Anonymous, different kinds of rehabilitation programs, and pharmacotherapy.

In the early 1970s, LSD-assisted psychotherapy had a positive effect on treatment outcome in heroin-addicted individuals. Later, ibogaine was shown to have anti-craving properties, but human research with it was halted due to concerns about toxicity.

We report our findings using KPT for heroin addiction in a double-blind protocol. The only available medication for heroin addiction in Russia is naltrexone, with its attendant problem of poor compliance.

2. Materials and methods

2.1. Design

Seventy detoxified heroin-addicted patients received psychotherapy in combination with a psychedelic dose of ketamine, or psychotherapy combined with a sub-psychedelic dose of ketamine. The low ketamine dose group was considered an ”active placebo”.

2.2. Subjects

All 70 subjects were recruited from the inpatient department of the Leningrad Regional Center of Addictions, and informed consent was obtained prior to acceptance into the study.

There were no statistically significant differences between the high dose and low dose groups with respect to age, duration of heroin addiction, or duration of abstinence from heroin.

The subjects participating in the study were mostly young adults, and the average duration of addiction was three to four years.

2.3. Psychotherapist

Psychotherapy was provided by a psychiatrist spe-cially trained in KPT. Only one KPT session was carried out for each subject. The details of KPTsessions and psychotherapeutic techniques are described below in Treatment Procedure.

2.4. Patient selection

The following inclusion and exclusion criteria were employed for patient selection:

2.4.1. Inclusion criteria

ICD-10/DSM-IV criteria for current heroin dependence present for at least one year, age between 18 and 30, high school education, and stable address in St. Petersburg or Leningrad region.

2.4.2. Exclusion Criteria

ICD-10/DSM-IV diagnosis of organic mental disorder, schizophrenic disorder, paranoid disorder, major affective disorder, or seizure disorder; family history of psychiatric disorders listed above; advanced neurological, cardiovascular, renal, or hepatic diseases; pregnancy; significant laboratory abnormalities.

2.5. Screening evaluation

The screening evaluation included: (1) a Formal psychiatric examination; (2) Completing the medical examination, including blood chemistry panel (including hepatic func-tions), urine analysis, HIV-test, pregnancy test, and EKG; and (3) a Review of previous medical and psychi-atric records.

2.6. Assessment instruments

2.7. Treatment assessment, outcome and follow-up

2.7.1. Assessment schedule

ZDS, SAS, VASC, SA, MMPI, LCS, CTA, and PLT were administered pre-therapy and post-therapy, and at 1, 3, 6, 12, 18 and 24 months after treatment was completed.

2.7.2. Follow-up data

Psychiatrists collected follow-up data on subjects for up to 24 months after ketamine therapy, if the subject had not relapsed. They were unable to follow subjects after they relapsed to heroin due to poor compliance.

2.8. Treatment procedure

All patients gave witness informed consent before inclusion into the study. Ten hours of psychotherapy were provided before the ketamine session and five hours of psychotherapy were provided after the ketamine session.

2.9. Description of the psychotherapeutic technique provided

The first stage of our method of KPT is preparation. During these sessions, we explain to the subjects that a ketamine session may induce insights concerning their personal problems, and possibly contribute to discovering their purposes in life.

During the ketamine sessions, subjects often experience an altered state, which has been described as the separation of consciousness from the body and the dissolving of the ego. The therapist pays close attention to the subject’s personal motives for treatment.

The second stage of KPT is the ketamine session itself, during which the subject is administered the assigned dose of ketamine and treated psychotherapeutically. This is done with the help of verbal influences and guiding the musical background toward the symbolic resolution of the personality conflicts.

The third stage of ketamine therapy involves special psychotherapeutic sessions. These sessions help the subject integrate the insights from the ketamine session into everyday life.

2.10. Data management and statistical analysis

Subject-related information was filed under a study code number for purposes of confidentiality and to maintain the double-blind design. The rate of abstinence and relapse was considered the primary outcome variable.

3. Results

3.1. Components of the ketamine experience

Acute psychological responses to the ketamine experience were evaluated using the Hallucinogen Rating Scale. High dose group patients had a full psychedelic experience, while low dose group patients experienced some drug effects.

3.2. Treatment outcome: Follow-up data for 24 months

The follow-up data showed that the high dose group had a higher rate of abstinence and a lower rate of relapse than the low dose group.

3.3. Craving for heroin

Ketamine significantly reduced craving for heroin in the high dose group, but not in the low dose group, and only for the first month in the low dose group.

3.4. Syndrome of anhedonia

In both high and low dose groups, KPT significantly reduced the severity of all three components of the syn-drome of anhedonia (Fig. 2). While scores for each subscales how a positive effect for the high dose group, the differences were not statistically significant.

3.5. Anxiety

Both KPT groups demonstrated significantly reduced anxiety compared to baseline, and the level of anxiety was within normal limits by 24 months.

3.6. Depression

Both high and low dose KPT significantly reduced elevated levels of pre-treatment depression relative to baseline values, measured by the Zung Depression Scale(Table 2). There were no significant differences between the two groups.

3.7. MMPI

High dose KPT decreased scores on the MMPI for depression, conversion hysteria, paranoia, schizophrenia, and the Taylor scale of anxiety. Low dose KPT increased scores on the MMPI for hypochondriasis, depression, and conversion hysteria.

3.8. Locus of control

The locus of control in heroin addicts became more internal after KPT in both groups, and the area of failures became more internal in the high dose group after KPT compared to baseline.

3.9. Understanding the meaning and purpose of one’sown life

Ketamine psychotherapy increased understanding of the meaning of life, purposes in life, self-actualization, and the ability to control one’s own life in accordance with those life purposes in the high dose group and low dose group, respectively.

3.10. Spirituality

The Spirituality Changes Scale showed that both high and low dose KPT groups of heroin addicts experienced an increase in spiritual development.

3.11. Non-verbal emotional attitudes

The methodology of the Color Test of Attitudes has been described in detail previously. The high dose KPT produced greater changes in nonverbal unconscious emotional attitudes of heroin addicts than did low dose KPT.

3.12. Side effects and complications

There were no complications, such as protracted psychosis or flashbacks, after KPT. No subject participating in the study became addicted to ketamine. The only side effect noted in all subjects was an acute increase in systolic and particularly diastolic blood pressure of 20–30% during the session.

4. Discussion

This double-blind, active-placebo controlled study demonstrated that ketamine-assisted psychotherapy of heroin addicts is more effective at high, psychedelic doses than at low, sub-psychedelic doses.

We confirm that acute psychological effects of ketamine in a sub-anesthetic dose are psychedelic in nature. The low dose group experienced something that functions as ketamine-facilitated guided imagery, but were often affected by their experiences and considered them as useful and therapeutic.

Subjects in the low dose group had experiences of what might be referred to as ”sub-psychedelic”, but higher than those seen in placebo groups in Strassman’s DMT and Bowdle’s ketamine studies. This may be due to the important interplay between set, setting, and dose of drug.

Ketamine psychotherapy produced no significant adverse reactions in this study, which is in distinct contrast to reports from the first phase of psychedelic psychotherapy studies with other compounds in 1960s.

The rate of abstinence in the high dose group was significantly greater than that of the low dose group, while the corresponding rate of relapse was lower. The high dose group also had a higher rate of abstinence than the typical rate of abstinence in conventional treatment programs.

High dose KPT produces greater and longer-lasting decrements in drug craving in heroin addicts than does low dose KPT.

Both groups showed a significant reduction in the severity of the syndrome of anhedonia, and the severity of all components of the syndrome was reduced, including the cognitive.

Both groups’ MMPI scores changed similarly, suggesting that patients became more confident, optimistic, less anxious, less depressed and neurotic, and more emotionally open after treatment.

Both groups demonstrated an increase in locus of control after treatment, with high dose KPT patients feeling more responsible for their lives.

The Purpose in Life Test data revealed that both groups demonstrated positive changes in life values of heroin addicts, reflecting the increased understanding and importance of life values other than the heroin ”high”.

A psychedelic ketamine experience is similar to the near-death experience (NDE) and may induce changes in spiritual development and worldview. Ketamine-assisted psychotherapy may represent one method of eliciting spiritual experiences in subjects with chemical dependence.

In a double-blind, randomized clinical trial of ketamine psychedelic psychotherapy for heroin addiction, high dose ketamine produced a significantly greater rate of abstinence within the first 24 months of follow-up than did low dose ketamine. Both treatment groups demonstrated changes in depression, anxiety, anhedonia, and psychological profile.

Acknowledgments

The authors are very grateful to the Multidisciplinary Association for Psychedelic Studies (MAPS, www.maps.org)and to the Heffter Research Institute (HRI, www.heffter.org)for their support of this study.