Single Versus Repeated Sessions of Ketamine-Assisted Psychotherapy for People with Heroin Dependence

Abstract

A prior study found that one ketamine-assisted psychotherapy session was significantly more effective than active placebo in promoting abstinence (Krupitsky et al. 2002). In this study of the efficacy of single versus repeated sessions of ketamine-assisted psychotherapy in promoting abstinence in people with heroin dependence, 59 detoxified inpatients with heroin dependence received a ketamine-assisted psychotherapy (KPT) session prior to their discharge from an addiction treatment hospital, and were then randomized into two treatment groups. Participants in the first group received two addiction counseling sessions followed by two KPT sessions, with sessions scheduled on a monthly interval (multiple KPT group). Participants in the second group received two addiction counseling sessions on a monthly interval, but no additional ketamine therapy sessions (single KPT group). At one-year follow-up, survival analysis demonstrated a significantly higher rate of abstinence in the multiple KPT group. Thirteen out of 26 subjects (50%) in the multiple KPT group remained abstinent, compared to 6 out of 27 subjects (22.2%) in the single KPT group (p < 0.05). No differences between groups were found in depression, anxiety, craving for heroin, or their understanding of the meaning of their lives. It was concluded that three sessions of ketamine-assisted psychotherapy are more effective than a single session for the treatment of heroin addiction.

Full text

Krupitsky et al. Ketamine Psychotherapy for Heroin Dependence
Journal of Psychoactive Drugs 13 Volume 39 (1), March 2007
Single Versus Repeated Sessions of
Ketamine-Assisted Psychotherapy for
People with Heroin Dependence†
Evgeny M. Krupitsky, M.D., Ph.D.*; Andrei M. Burakov, M.D., Ph.D.**;
Igor V. Dunaevsky, M.D., Ph.D.***; Tatyana N. Romanova, M.S.****;
Tatyana Y. Slavina, M.D., Ph.D.***** & Alexander Y. Grinenko M.D., Ph.D.******
Abstract— A prior study found that one ketamine-assisted psychotherapy session was signicantly
more effective than active placebo in promoting abstinence (Krupitsky et al. 2002). In this study of the
efcacy of single versus repeated sessions of ketamine-assisted psychotherapy in promoting abstinence
in people with heroin dependence, 59 detoxied inpatients with heroin dependence received a ketamine-
assisted psychotherapy (KPT) session prior to their discharge from an addiction treatment hospital, and
were then randomized into two treatment groups. Participants in the rst group received two addiction
counseling sessions followed by two KPT sessions, with sessions scheduled on a monthly interval
(multiple KPT group). Participants in the second group received two addiction counseling sessions
on a monthly interval, but no additional ketamine therapy sessions (single KPT group). At one-year
follow-up, survival analysis demonstrated a signicantly higher rate of abstinence in the multiple KPT
group. Thirteen out of 26 subjects (50%) in the multiple KPT group remained abstinent, compared to
6 out of 27 subjects (22.2%) in the single KPT group (p < 0.05). No differences between groups were
found in depression, anxiety, craving for heroin, or their understanding of the meaning of their lives. It
was concluded that three sessions of ketamine-assisted psychotherapy are more effective than a single
session for the treatment of heroin addiction.
Keywords—hallucinogens, heroin addiction, ketamine, psychedelics, psychotherapy, treatment
†This study was supported by the Multidisciplinary Association for
Psychedelic Studies (MAPS), Sarasota, Florida, USA and by the Heffter
Research Institute, Santa Fe, New Mexico, USA. The authors are also very
thankful to Rick Doblin, Lisa Jerome, Valerie Mojeiko, and Dr. George
Greer for assistance in editing the manuscript, and to Tatyana Volskaya,
M.A., for data management.
*Chief of the Research Laboratory, St. Petersburg Regional Center of
Addictions and Psychopharmacology, St. Petersburg State Pavlov Medical
University, St. Petersburg, Russia.
**Psychiatrist, St. Petersburg Regional Center of Addictions and
Psychopharmacology, St. Petersburg State Pavlov Medical University, St.
Petersburg, Russia.
***Anesthesiologist, St. Petersburg Regional Center of Addictions
and Psychopharmacology, St. Petersburg State Pavlov Medical University,
St. Petersburg, Russia.
****Clinical Psychologist, St. Petersburg Regional Center of
Addictions and Psychopharmacology, St. Petersburg State Pavlov Medical
University, St. Petersburg, Russia.
*****Psychiatrist and Medical Director, St. Petersburg Regional
Center of Addictions and Psychopharmacology, St. Petersburg State Pavlov
Medical University, St. Petersburg, Russia.
******Director, St. Petersburg Regional Center of Addictions and
Psychopharmacology, St. Petersburg State Pavlov Medical University, St.
Petersburg, Russia.
Please address correspondence and reprint requests to Evgeny M.
Krupitsky, M.D., Ph.D., St. Petersburg Regional Center of Addictions and
Psychopharmacology, Novo-Deviatkino 19/1, Leningrad Region 188661,
Russia. Email: kru@ek3506.spb.edu
Psychedelic-assisted psychotherapy utilizes the acute
psychological effects of psychedelic, or hallucinogenic,
drugs to enhance the normal mechanisms of psychotherapy.
Many studies carried out in the 1950s and 1960s suggested
that psychedelic-assisted psychotherapy might be an efcient
treatment for alcoholism and addictions (Grinspoon &
Bakalar 1979). However, it is difcult to generalize across
these studies because of differences in methodology. After
they were scheduled in 1970, the use of psychedelic drugs
in research was strictly limited, signicantly curtailing

Krupitsky et al. Ketamine Psychotherapy for Heroin Dependence
Journal of Psychoactive Drugs 14 Volume 39 (1), March 2007
the development of studies employing more sophisticated
methods. However, data collected in the 1950s and 1960s
provide some important insights about treatment effects of
psychedelic psychotherapy, which have been summarized
in Halpern’s (1996) comprehensive review.
One of the insights gained from previous research
concerns the transient psychotherapeutic and psychologi-
cal effects of psychedelic psychotherapy. The effects of
psychedelic psychotherapy are often very pronounced
within several days or weeks after a treatment session, but
then these effects quickly decline (Halpern 1996). This
phenomenon was termed a “psychedelic afterglow.” Pahnke
and colleagues (1970) described an afterglow as a positive
post-hallucinogen state occurring in subjects after they have
a transcendent psychedelic peak experience:
If a psychedelic-peak experience has been achieved and sta-
bilized during the session, a clinical picture which we have
termed the psychedelic afterglow can be observed in the days
after the session. Mood is elevated and energetic; there is a
relative freedom from concerns of the past and from guilt and
anxiety, and the disposition and capacity to enter into close
interpersonal relationships is enhanced. These psychedelic
feelings generally persist for from two weeks to a month and
then gradually fade into vivid memories that hopefully will
still inuence attitude and behavior. During this immediate
postdrug period, there is a unique opportunity for effective
psychotherapeutic work on strained family or other interper-
sonal relationships.
Ketamine is a drug used for anesthesia that acts as an
NMDA receptor antagonist. Sub-anesthetic doses produce
profound transformative experiences that share many ele-
ments with some near-death experiences (Jansen 2001).
Previous studies have found that this experience often causes
important insights about the self and the world, and can help
people accept a new meaning of life, new values and new
purpose in life related to abstinence from drugs and alcohol
(Krupitsky et al. 2002; Krupitsky & Grinenko 1997).
Recent studies that employed a single-session ketamine
psychotherapy (KPT) paradigm for alcohol and heroin-de-
pendent patients have demonstrated that KPT is an effective
treatment in promoting abstinence in alcoholics (Krupitsky
& Grinenko 1997) and heroin addicts (Krupitsky et al. 2002).
However, these studies did not clarify whether the effect of
a single KPT session might be further enhanced by repeated
sessions.
The major aim of this study was to compare the efcacy
of a single session of ketamine-assisted psychotherapy with
a multiple (three session) KPT regime in people with heroin
dependence. The authors sought to determine whether the
repeated sessions of KPT carried out over one-month inter-
vals would improve the efcacy of a single KPT session, as
reected in objective measures of treatment outcome, such
as abstinence from heroin on follow-up. In other words,
could the efcacy of KPT in treating heroin dependence be
increased by administering multiple KPT sessions and thus
stabilizing the afterglow?
MATERIAL AND METHODS
Design
After detoxication, 59 heroin-dependent participants
were assigned to one of two groups on a random selection ba-
sis. The randomization was done after the rst KPT session,
but prior to the second session of KPT or counseling.
The participants in the multiple KPT group received
three KPT sessions with a psychedelic (hallucinogenic)
dose of ketamine (2.0 mg/kg i.m.), with one-month intervals
between sessions. They received their rst KPT session as
inpatients after detoxication, just before being discharged
from a psychiatric hospital. They came to the same hospi-
tal one and two months later for the second and third KPT
sessions as outpatients. An individual addiction counseling
session was conducted every time before the repeated (sec-
ond and third) KPT sessions.
The participants in the single KPT group received
only one KPT session with the same dose of ketamine and
the same psychotherapeutic technique and environment as
participants in the multiple KPT group. They received the
KPT session as inpatients after detoxication, prior to being
discharged from the psychiatric hospital. After one and two
months, the same psychotherapist who carried out the KPT
conducted an individual addiction counseling session at the
psychiatric hospital.
All participants were treated alike and were given the
same preparation for KPT. The KPT sessions, regardless
of their number, were given under uniform circumstances
at the same psychiatric hospital. Clinical evaluators blind
to whether participants had received one or three KPT ses-
sions performed psychological and clinical evaluations on
all participants during treatment and follow-up periods.
Participants
Out of 73 heroin-dependent patients screened, 59 of
them (mean age M ± SD = 22.6 ± 3.9 years, duration of
heroin abuse 38.8± 30.4 months, 49 males and 10 females)
met inclusion criteria and were included in the study. Par-
ticipants were recruited from the inpatient department of
the Leningrad Regional Center of Addictions, a 300-bed
hospital for treating patients with alcoholism and chemi-
cal dependencies who are living in the Leningrad Region.
Informed consent was obtained from all participants prior
to acceptance into the study. The study was approved by the
Human Experimentation Ethical Committee at St. Petersburg
Pavlov State Medical University.
Psychotherapist
A psychotherapist specially trained by the investiga-
tor in conducting KPT provided psychotherapy to study

Krupitsky et al. Ketamine Psychotherapy for Heroin Dependence
Journal of Psychoactive Drugs 15 Volume 39 (1), March 2007
participants. All KPT and addiction counseling sessions for
participants in both single and multiple KPT groups were
done by the same psychotherapist.
Participant Selection
The following exclusion and inclusion criteria were
employed for participant selection:
•Inclusion criteria: ICD-10/DSM-IV criteria of current
heroin dependence present for at least one year; age
between 18 and 35; at least high school education;
abstinence from heroin and other substances of abuse
for at least two weeks; not currently on psychotropic
medication; at least one relative willing to assist in
follow-up and provide outcome data; stable address
within St. Petersburg or nearest district of Leningrad
Region; participant has a home telephone number at
which he/she can be reached; not currently on proba-
tion; and competency to give informed consent and
otherwise participate.
•Exclusion criteria: ICD-10/DSM-IV criteria of organic
mental disorder, schizophrenic disorder, paranoid
disorder, major affective disorder, or seizure disorder;
ICD-10/DSM-IV criteria for alcoholism or polydrug
dependency; advanced neurological, cardiovascular,
renal, or hepatic diseases; pregnancy; family history of
psychiatric disorders listed above; clinically signicant
cognitive impairment; active tuberculosis or current
febrile illness; AIDS; signicant laboratory abnormal-
ity such as severe anemia, unstable diabetes, or liver
function tests more than three times above normal;
pending legal charges with potential impending incar-
ceration; concurrent participation in another treatment
study; or concurrent treatment in another substance
abuse program.
Participant’s Evaluation
The participant’s evaluation included a formal psychi-
atric and clinical examination and a battery of psychiatric
and psychological scales.
Formal psychiatric and clinical examination included a
standard medical examination, with blood chemistry panel
(including hepatic functions), urine analysis, pregnancy
test, electrocardiogram, and review of previous medical and
psychiatric records.
The psychological assessment consisted of two parts,
psychiatric assessments and psychological assessments.
Psychiatric symptoms were assessed with Zung Self-Rated
Depression Scale (ZDS; Zung 1965), Spielberger Self-Rated
State-Trait Anxiety Scale (SAS; Spielberger et al. 1976),
and the Visual Analog Scale of Craving for Heroin (VASC;
Krystal et al. 1998). Psychological assessment consisted of
the Purpose-in-Life Test (PLT; Crumbaugh 1968) based on
Frankl’s (1978) concept of people’s aspiration for the mean-
ing of life, intended to assess the participant’s understanding
of the meaning of his/her life. All international rating scales
mentioned above had been specially adapted and validated
in Russia before the study.
Treatment Assessment, Outcome and Follow-Up
During the treatment phase, the investigators performed
urine drug testing before the rst KPT session in both groups,
before each successive KPT and counseling session in the
multiple KPT group, and before each addiction counseling
session in the single KPT group. The ZDS, SAS, VASC, and
PLT were administered before and after the rst KPT session
in both groups, before and after the second and third KPT
and addiction counseling sessions in the multiple KPT group,
and before and after each of the two addiction counseling
sessions in the single KPT group.
One month after the nal treatment, and then at three-
month intervals for the remainder of the year, participants
completed a follow-up interview in person with a research
assistant. Each participant underwent a physical examina-
tion to determine the presence or absence of traces (marks)
of injections on his or her veins, and a urine sample was
collected for drug testing. Information from the physical
examination was used to determine whether a participant
had abstained from heroin. Abstinent participants completed
the ZDS, SAS, VASC, and PLT during this examination.
In addition, psychiatrists blind to condition collected
follow-up data on a monthly basis for up to 12 months after
the end of the treatment phase (the last session). During
monthly telephone interviews, the psychiatrists collected
self-reported information from the participant about his/her
drug use during the follow-up period, using the Time Line
Follow Back technique (Sobell & Sobell 1992). Information
from the participant’s relatives about the participant’s drug
use was collected in the same manner.
Treatment Procedure
Before the rst ketamine session, participants received
ve hours of psychotherapy focused on the participants’
addictions to prepare them for the ketamine session, and
they received ve hours of psychotherapy after the rst
ketamine session to help them to interpret their experience
during the ketamine session and integrate it into everyday
life. One hour of addiction counseling was provided before
the second and third KPT sessions to prepare participants
to explore issues related to their chemical dependence
during those sessions. After the second and third KPT ses-
sions, participants in the multiple KPT group received an
additional hour of psychotherapy after each session to help
them integrate their experience during these sessions.
An anesthesiologist was available throughout all ket-
amine sessions to treat any possible complications. Ketamine
was injected intramuscularly at the dose of 2 mg/kg. The
length of a ketamine session was between 1.5 and two hours.
The participant was instructed to recline on a couch with eye-
shades. The participant listened to a preselected program of
music throughout the session. The psychotherapist provided

Krupitsky et al. Ketamine Psychotherapy for Heroin Dependence
Journal of Psychoactive Drugs 16 Volume 39 (1), March 2007
emotional support for the participant and carried out psycho-
therapy during the ketamine session. The psychotherapy was
existentially-oriented, focusing on assisting the participant
to consider and formulate a purposeful or meaningful life,
but also took into account the participant’s individuality,
and his or her specic personality problems. This therapy
aimed to establish a strong personal motivation for a sober
life without drugs.
The ketamine experience is similar to some near-death
experiences (Jansen 2001), and it may produce a positive
shift in the participant’s understanding of the meaning
of life, life purposes, and spiritual development through
mechanisms similar to those seen with near-death experi-
ences (Krupitsky et al. 2002; Krupitsky & Grinenko 1997).
The major goal of the psychotherapy provided before, dur-
ing, and after KPT sessions was to assist the participant in
reaching this positive shift. The details of KPT technique
and psychotherapeutic intervention have been described in
previous publications (Krupitsky et al. 2002; Krupitsky &
Grinenko 1997).
Ketamine produces diverse experiences ranging from
spiritual rapture to fear and even horror, sometimes all in
the same person and during the same session. People have
reported experiencing violent or rapid travel through tunnels
or corridors, derealization, extreme depersonalization asso-
ciated with intense fear or euphoria, and feeling connected
to God or a higher power. The transformative experiences
often began with extreme fear, including fear of the world
ending or apocalypse, and often ended in an experience of
rebirth associated with oceanic, or positively experienced,
ego loss and boundlessness. All of these experiences were
emotionally intense and compelling. Many people reported
great difculty in expressing their experiences in words. It
should be noted that despite these common themes, the pa-
tient almost always experienced individually specic themes
that reected the individual’s case history and personality
problems in symbolic form.
After the rst KPT session, all participants received
an addiction counseling session at their second and third
monthly scheduled appointments. These sessions included
manualized addiction counseling procedures used in Rus-
sia, which include elements of cognitive-behavioral therapy
and a motivational enhancement approach. Participants in
the multiple KPT group also received brief instructions
preparing them for additional KPT during these addiction
counseling sessions.
Data Management and Statistical Analysis
Data management and analysis were performed with
SPSS 11.0 statistical software package. The rate of absti-
nence was considered the primary outcome variable. The
psychometric data were treated as secondary outcome
variables, with each scale considered independent of other
scores. Survival analysis (Kaplan-Meier survival function)
was employed to assess differences in the rate of abstinence
between the single and multiple KPT groups.
FIGURE 1
Kaplan-Meier Survival Analysis
P < 0.01

Krupitsky et al. Ketamine Psychotherapy for Heroin Dependence
Journal of Psychoactive Drugs 17 Volume 39 (1), March 2007
MANOVA within-subjects repeated measures of analy-
sis design with Tukey test for post-hoc comparisons were
employed to assess the effect of single versus repeated KPT
and counseling sessions and changes in psychometrics over
the treatment and follow-up periods. Independent variables
were participant’s condition (single or multiple KPT) and
follow-up time point, and dependent variables were ZDA,
SAS, VASC, and PLT scores.
RESULTS
Retention in Treatment and Abstinence Rate
Six out of 59 participants enrolled in the study (mean
age M ± SD = 23.0 ± 5.5 years, duration of heroin abuse
48.3 ± 48.0 months, ve males and one female) relapsed
and dropped out of treatment within the rst month after the
initial KPT session. Prior to the second session, the 53 re-
maining participants were randomized into the two treatment
groups. Twenty-six participants (mean age M ± SD = 22.4
± 4.1 years, duration of heroin abuse 36.5 ± 27.6 months,
21 males and ve females) were assigned to the multiple
KPT group and received two more KPT sessions, includ-
ing addiction counseling sessions before KPT, separated by
one-month intervals. Twenty-seven participants (mean age
M ± SD = 22.7 ± 3.5 years, duration of heroin abuse 38.9 ±
29.2 months, 23 males and four females) were assigned to
the single KPT group and received two addiction counseling
sessions separated by one-month intervals. There were no
statistically signicant differences between these groups in
the mean age, duration of heroin addiction, and gender.
In the multiple KPT group, four out of 26 participants
(15.4%) relapsed and dropped out of treatment after the
second KPT session but prior to the third. In the single KPT
group, seven out of 27 participants (25.9%) relapsed and
dropped out of treatment after the rst counseling session.
The difference in the retention in treatment phase between
the two groups was not statistically signicant.
However, Kaplan-Meier survival analysis revealed sta-
tistically-signicant differences in the follow-up abstinence
rate between groups: the abstinence rate was signicantly
greater in the multiple KPT group throughout the year of the
follow-up (Figure 1). At the end of the one-year follow-up,
13 out of 26 participants (50%) in the multiple KPT group
remained abstinent compared to six out of 27 participants
(22.2%) in the single KPT group (p < 0.05).
Psychometrics
Symptom intensity for all measures administered
(depression, state and trait anxiety, and craving for heroin)
were signicantly reduced after the rst KPT session in both
groups, and then gradually decreased further in both groups
in those participants who did not relapse and who showed
up for scheduled appointments. There were no signicant
differences in these scores between the single and multiple
KPT groups (see Table 1). Those who relapsed were
unavailable for psychometric evaluation. The understand-
ing of the meaning of life measured by the PLT improved
in both groups in a similar manner (Table 1), and there were
no statistical differences between the two groups.
Side Effects
There were no complications, such as protracted psy-
chosis or ashbacks, after KPT. No participant taking part in
the study became addicted to ketamine. The only side effect
noted in all participants was an acute increase in systolic and
particularly diastolic blood pressure of 20% to 30% during
the ketamine psychotherapy session.
DISCUSSION
Results of this study showed that a three session KPT
program is more effective in promoting abstinence from
heroin addiction than a single KPT session followed by two
counseling sessions. The rate of abstinence was signicantly
higher in the three KPT session group throughout a year of
follow-up. At the end of one year, the rate of abstinence
in the multiple KPT sessions group (50%) was more than
twice as high as in the single KPT session group (22.2%).
Furthermore, if we include the six participants who relapsed
after a single KPT session but prior to condition assignment
into the single KPT group, it lowers the rate of abstinence at
12 months to 18.2%, lending further support to the conten-
tion that a single KPT session does not provide the same
benets as multiple KPT sessions. These results correspond
very well with the observations made in clinical studies
with psychedelics carried out in the 1950s and 1960s that
provided the rationale for the multiple session approach
used in this study. In particular, Halpern (1996) noted that,
“the longer follow-up, the less improvement was observed
across the single dose studies.” In the review of Grinspoon
and Bakalar (1979), the authors wrote that “Some controlled
studies show an improvement lasting from several weeks
to several months . . . The obvious recourse of supplemen-
tary treatments every once in a while has been suggested
but never taken seriously possibly because everyone is
mesmerized by the vision of a quasi-miraculous single-
shot cure . . .”
This study does not compare ketamine-assisted therapy
with placebo, raising issues of separating effects resulting
from ketamine-assisted therapy versus those arising from
psychotherapy or from placebo effect. However, a previ-
ous investigation we conducted has addressed this issue,
nding that high-dose ketamine produced a greater rate of
abstinence from heroin than psychotherapy conducted with
active placebo (Krupitsky et al. 2002). Building on these
ndings, we chose to examine whether multiple (three)
psychotherapy sessions could produce greater benets than
a single session.
It is interesting to note that the 22.2% rate of abstinence
after one year in the single KPT session group in this study

Krupitsky et al. Ketamine Psychotherapy for Heroin Dependence
Journal of Psychoactive Drugs 18 Volume 39 (1), March 2007
TABLE 1
Psychometric data
Psychometrics by Time Points (M±SE)
Symptom Group 1st Session 2nd Session 3rd Session Follow-ups
Before After Before After Before After 1st Month 3rd Month 6th Month 9th Month 12th Month
Depression 1st 41.2± 36.9± 36.6± 37.5± 35.6± 34.5± 35.1± 34.3± 36.7± 37.4± 34.3±
1.5 1.4 1.3 1.6 1.5 1.4 1.4 1.4 1.7 1.8 1.4
2nd 44.7± 39.9± 40.8± 38.0± 35.8± 35.0± 35.4± 36.8± 34.5± 37.9± 30.6±
2.0 1.8 2.0 1.6 1.3 1.3 1.6 1.3 1.2 1.3 0.7
State anxiety 1st 43.8± 38.4± 38.9± 37.0± 34.6± 33.4± 33.0± 32.6± 34.8± 33.7± 30.6±
1.9 2.2 2.2 1.7 1.7 1.3 1.6 1.7 2.1 1.9 1.8
2nd 42.7± 39.9± 39.6± 38.4± 35.3± 33.3± 33.0± 32.5± 31.1± 32.4± 28.1±
1.5 1.8 1.6 1.8 1.0 1.3 1.7 1.3 1.4 1.4 0.6
Trait anxiety 1st 42.0± 34.4± 33.8± 32.0± 33.2± 29.9± 30.4± 26.9± 31.6± 29.6± 25.8±
2.0 2.3 1.9 1.8 2.4 1.6 1.7 1.1 2.0 1.4 1.3
2nd 41.5± 33.3± 36.4± 34.3± 31.15± 29.2± 30.5± 29.6± 26.4± 23.6± 24.7±
1.9 1.6 2.0 1.9 1.5 1.3 1.9 1.1 1.6 0.8 0.5
Craving for heroin 1st 20.1± 9.6± 11.9± 6.07± 7.1± 5.4± 6.09± 2.6± 5.3± 3.2± 0.3±
4.7 3.6 3.5 2.7 3.1 3.0 2.6 1.0 2.1 1.7 0.2
2nd 22.8± 4.6± 8.9± 7.3± 4.7± 3.3± 7.2± 3.7± 3.9± 1.9± 0.0±
5.4 1.6 3.3 2.8 1.5 1.1 2.9 1.4 1.3 0.5 0.0
Understanding 1st 92.0± 106.5± 108.8± 110.3± 112.8± 113.8± 115.2± 115.2± 114.9± 115.7± 119.6±
the meaning 3.6 3.6 3.2 2.9 3.1 2.6 3.7 3.3 2.8 3.8 3.4
of life 2nd 90.3± 101.6± 103.0± 103.3± 113.6± 113.5± 114.9± 115.1± 120.5± 119.8± 124±
3.6 3.6 3.7 4.1 2.8 2.7 3.4 3.2 2.3 2.7 0.8
Notes: First group — multiple KPT, second group — single KPT. MANOVA results: All the psychometrics signicantly improved over the time points. No signicant
differences in either one psychometric were found between the rst and the second group.

Krupitsky et al. Ketamine Psychotherapy for Heroin Dependence
Journal of Psychoactive Drugs 19 Volume 39 (1), March 2007
was similar to the one year abstinence rate of 24% after a
single KPT session in a previous study of KPT for heroin
addiction (Krupitsky et al. 2002), in which a single KPT
session was compared to a single active placebo session (a
low, nonpsychedelic dose of ketamine). Due to the close
similarities in rate of one year abstinence in the single KPT
groups in this current study and in the previous study, it
seems likely that the groups are well-matched. This supports
the assumption that, were a placebo group to have been
added to this current study, the rate of one year abstinence
would have been somewhat similar to that in the earlier
study, or 6%. It is also notable that the rate of abstinence
for single KPT participants was similar to the rate of reten-
tion in treatment for people receiving the opioid antagonist
naltrexone (Krupitsky et al. 2004), and the rate of abstinence
in the multiple KPT was even higher than after naltrexone
treatment. These ndings suggest that multiple sessions of
KPT hold promise as a treatment for people with heroin
dependence, and that multiple sessions are better than a
single session of KPT, despite lack of signicant differences
between the two groups in self-reported depression, anxiety
or cravings for heroin.
The lack of signicant differences between single and
multiple KPT groups on other outcome measures, includ-
ing those for depression, anxiety, life purpose and heroin
craving, suggests that increased rates of abstinence in the
multiple KPT group is at least partly due to factors not mea-
sured in this study. This effect could be related to a specic
shift in the participant’s mind and his or her attitude to life
that was described by Pahnke and colleagues (1970) as an
“afterglow,” and for which we do not yet have a rating scale
to measure. In the future, we may employ measures more li-
able to capture this shift or change in attitude or life view.
REFERENCES
Crumbaugh, J.S. 1968. Cross-validation of Purpose-in-Life Test based on
Frankl’s concept. Journal of Individual Psychology 24: 74-81.
Frankl, V. 1978. The Unheard Cry for Meaning. New York: Simon and
Schuster.
Grinspoon, L. & J. Bakalar. 1979. Psychedelic Drugs Reconsidered. New
York: Basic Books.
Halpern, J. 1996. The use of hallucinogens in the treatment of addiction.
Addiction Research 4: 177-89.
Jansen, K. 2001. Ketamine: Dreams and Realities. Sarasota, FL: MAPS.
Krupitsky, E. & Grinenko, A.Y. 1997. Ketamine psychedelic therapy
(KPT): A review of the results of ten years of research. Journal of
Psychoactive Drugs 29: 165-83.
Krupitsky, E.; Zvartau, E.; Masalov, E.; Tsoi, M.; Burakov, A.; Egorova,
V.; Didenko, T.; Romanova, T.; Ivanova, E.; Bespalo, A.; Verbitskaya,
E.; Neznanov, N.; Grinenko, A.; O’Brien, C. & Woody, G. 2004.
Naltrexone for heroin dependence treatment in St. Petersburg, Russia.
Journal of Substance Abuse Treatment 26: 285-94.
Krupitsky, E.; Burakov, A.; Romanova, T.; Dunaevsky, I.; Strassman, R. &
A. Grinenko, A. 2002. Ketamine psychotherapy for heroin addiction:
Immediate effects and two-year follow-up. Journal of Substance
Abuse Treatment 23: 273-83.
Krystal, J.H.; Petrakis, I.L.; Webb, E.; Cooney, N.L.; Karper, L.P.;
Namanworth, S.; Stetson, P.; Trevisan, L.A. & Charney, D.S. 1998.
Dose-related ethanol-like effects of the NMDA antagonist, ketamine,
in recently detoxied alcoholics. Archives of General Psychiatry
55: 354-60.
Pahnke, W.; Kurland, A.; Unger, S.; Savage, C. & Grof, S. 1970. The
experimental use of psychedelic (LSD) psychotherapy. Journal of
the American Medical Association 212: 1856-63.
Sobell, L. &. Sobell, M. 1992. Timeline Follow-Back: A technique for
assessing self-reported alcohol consumption. In: R. Litten & J. Allen
(Eds.) Measuring Alcohol Consumption [city?]: The Human Press.
Spielberger, C.S.; Gorsuch, R.L. & Lushene, R.E. 1976. Manual for the
State Trait Anxiety Inventory. Palo Alto, CA: Consulting Psychologists
Press.
Zung, W. 1965. A self-rating depression scale. Archives of General
Psychiatry 12: 63-70.