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


Abstract and Figures

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.
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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:
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
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?
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.
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.
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.
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.
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).
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.
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
Psychometric data
Psychometrics by Time Points (M±SE)
Symptom Group 1
Session 2
Session 3
Session Follow-ups
Before After Before After Before After 1
Month 3
Month 6
Month 9
Month 12
Depression 1
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
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 1
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
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 1
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
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 1
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
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 1
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 2
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.
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... According to different pre-clinical and human studies that examined the effect of ketamine in SUD, experts have argued that ketamine may block reconsolidation of drugrelated memories (Das et al., 2013;Zhai et al., 2008), provoke peak or mystical-type experiences that enhance psychotherapeutic process and lead to profound perspective shifts (Krupitsky et al., 2002;Krupitsky et al., 2007;Morgan et al., 2017) This latter hypothesis underpinned Dakwar and colleagues" method of administration, which combined ketamine with a psychotherapeutic intervention (MET) in patients suffering from alcohol dependence. The treatment rationale was based on the hypothesis that the behavioral-psychological intervention would act synergistically to consolidate the transient motivational and neuroplastic benefits of ketamine into more sustained change, as supported by the promising results the authors have observed previously with ketamine in cocaine use disorder (Dakwar et al., 2019). ...
... It is J o u r n a l P r e -p r o o f 23 worth mentioning that Dakwar and colleagues demonstrated in a recent article that the improvements in drinking behaviors were mediated by the mystical-type psychoactive effects of ketamine (Rothberg et al., 2021), rather than other perceptual effects such as dissociation. This finding is in line with the therapeutic framework of the previous "psychedelic" investigations by Krupitsky and colleagues in the late 1990"s (Krupitsky et al., 2002;Krupitsky et al., 2007;Morgan et al., 2017). ...
... The psychedelic model emphasizes the importance of the subjective ketamine experiences, in line with the early research of the 1960"s using psychoactive drugs like LSD and psilocybin to treat alcoholism (Greenway et al., 2020) In this framework, the experiences generated by ketamine are posited to increase awareness of unconscious processes that sustain addiction, produce aversions to alcohol, enhance self-compassion, generate insight-bestowing "breakthrough" realizations, modify worldviews, and/or increase feelings of "connectedness" with self and beyondall of which may enhance chances of overcoming addiction (Kolp et al., 2006;Krupitsky et al., 2002;Krupitsky et al., 2007;Krupitsky and Grinenko, 1997). Psychedelic treatment protocols embed the drug experiences in psychotherapy, being preceded by preparatory and followed by integrative sessions (Kolp et al., 2014). ...
Background Alcohol use disorder is highly prevalent and has important economical, societal, psychiatric, and medical consequences. All currently approved therapeutic approaches targeting alcohol dependence have relatively modest effects and high relapse rates. Recent evidence suggests that ketamine may be an effective intervention to treat alcohol use disorder and alcoholic withdrawal. This systematic review aimed to assess the current level of evidence for this intervention. Methods This systematic review was carried out following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and was registered on the international database of systematic reviews PROSPERO. Medline(Ovid), CINAHL Complete(EBSCOhost), PsycINFO(Ovid), EBM Reviews(Ovid), EMBASE(Ovid), and Google Scholar were searched for studies using ketamine to treat harmful alcohol use, craving, or withdrawal states in humans. Studies of any methodology that evaluated ketamine in isolation or combination with other interventions were included. The risk of bias was assessed using specific Cochrane critical appraisal tools. Results Of 1922 abstracts identified, 8 full-text articles were eligible for inclusion, yielding a total sample size of 634 participants. Five studies investigated the impact of ketamine on alcohol use and/or cravings and/or withdrawal in outpatient settings. Three studies looked at the effect of adding ketamine to conventional treatment of withdrawal symptoms in participants admitted to intensive care unit for severe alcohol withdrawal. Results on primary outcomes were mixed within and across trials. Conclusions Despite promising results, the current evidence does not permit definitive conclusions about the efficacy of ketamine in alcohol use disorders or withdrawal. Future studies are warranted.
... Ketamine treatment has also demonstrated efficacy for patients with other mental illnesses besides MDD. It has been shown to reduce anxiety symptoms in patients with generalized anxiety disorder (GAD) and/or social anxiety disorder (SAD) [6][7][8], and preliminary evidence shows that ketamine treatment may reduce symptoms of substance use disorders [9][10][11][12], post-traumatic stress disorder (PTSD) [13], bipolar depression [14], and eating disorders [15]. ...
... The PHQ-9 asks patients to rate the frequency of the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition's (DSM-V) symptoms of MDD over the past 2 weeks [33]. The PHQ-9 total score ranges from 0 to 27, with scores representing minimal depression (0-4), mild depression (5-9), moderate depression (10)(11)(12)(13)(14), moderately severe depression (15)(16)(17)(18)(19), and severe depression (20)(21)(22)(23)(24)(25)(26)(27). Item 9 of the PHQ-9 is a brief SI measure. ...
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Background: Ketamine has emerged as a promising pharmacotherapy for depression and other mental illnesses, and the intramuscular (IM) administration of ketamine is now offered at many North American outpatient psychiatric clinics. However, a characterization of the outpatient population receiving IM ketamine treatment and an evaluation of the real-world depression, anxiety, and safety outcomes of long-term psychiatric IM ketamine treatment has not been reported. This study aimed to evaluate the clinical characteristics, treatment patterns, clinical outcomes, and adverse events of patients receiving IM ketamine treatment. Methods: Patient data from the electronic health records of a private outpatient psychiatric clinic network in the United States were collected and analyzed retrospectively. Adults with any psychiatric diagnosis who received ketamine treatment only by IM administration from January 2018 to June 2021 were included. A total of 452 patients were included in the cohort. Results: Patients receiving IM ketamine treatment had a mean of 2.8 (SD 1.4) psychiatric diagnoses. 420 (93%) patients had a diagnosis of major depressive disorder, 243 (54%) patients had a diagnosis of generalized anxiety disorder, and 126 (28%) patients had a diagnosis of post-traumatic stress disorder. Patients received a median of 4 (range 1-48) IM ketamine treatments. Median depression scores (PHQ-9) improved 38% from 16.0 (IQR 11.3-21.8) at baseline to 10.0 (IQR 6.0-15.0) at last treatment (p < .001). Median anxiety scores (GAD-7) improved 50% from 14.0 (IQR 8.0-17.0) at baseline to 7.0 (IQR 4.3-11.8) at last treatment (p < .001). With maintenance ketamine treatments, average improvements in depression (PHQ-9) and anxiety (GAD-7) scores of at least 4.7 and 4.9 points were maintained for over 7 months. An adverse event occurred during 59 of 2532 treatments (2.3%). Conclusions: IM ketamine is being utilized to treat psychiatric outpatients with multiple mental illnesses not limited to depression. Average depression and anxiety levels significantly improve throughout IM ketamine treatment and do not regress to baseline during patients' maintenance treatment phase. Prospective studies are recommended to confirm the long-term effectiveness and safety of IM ketamine.
... Despite this, in recent decades there has been a renewed interest in NMDAR antagonists and their potential therapeutic usage for numerous CNS disorders, resulting in a plethora of research investigating numerous possible applications. Such applications have included treatments for MHDs such as treatment-resistant depression (Mathew and Zarate Jr, 2016), posttraumatic stress disorder (e.g., (Feder et al., 2021)), obsessive compulsive disorder (e.g., (Martinotti et al., 2021)), eating disorders (Keeler et al., 2021;Ragnhildstveit et al., 2021) and substance use disorder (e.g., (Krupitsky et al., 2007)) as well as treatments for neurodegenerative diseases such as Alzheimer's (e.g., (Liu et al., 2019)). Based on the emerging literature but limited clinical experience these drugs seem to have potential for biomedical research and positive therapeutic outcomes. ...
... (Grob and Grigsby, 2021;Winkelman and Sessa, 2019)) was made early on. Furthermore, in the 1980s and 1990s, the use of ketamine for treating alcoholism, heroin-dependence, and anxiety was studied in Russia by Krupitsky and colleagues (Krupitsky et al., 2002;Krupitsky et al., 2007;Krupitsky and Grinenko, 1997). ...
The so-called “psychedelic renaissance” has stimulated expanded interest in several classes of drugs that appear to possess transdiagnostic effects in the treatment of mental health disorders, specifically. N-methyl-d-aspartate receptor (NMDAR) antagonists are one such class with diverse therapeutic potential. NMDARs mediate excitatory postsynaptic signalling in the central nervous system (CNS) and are integral to normal neurobiological processes including neuronal development, synaptic transmission, and plasticity, and thus involved in learning and memory. However, NMDAR hyper-function is also implicated in acute CNS trauma, neuropsychiatric and neurodegenerative disorders, as well as chronic pain. The complex structure of NMDARs permits several locations for therapeutic inhibition, making these receptors a potential target for multiple drugs which modulate them in different ways. NMDAR antagonists, which may be competitive, non-competitive, or uncompetitive, either block glutamate from binding the receptor or modulate the response to glutamate binding. Despite longstanding concerns about side effects of NMDAR antagonists, recent research suggests that, when appropriately used, these agents have favourable safety profiles. Furthermore, their fast-acting mechanism of action, resulting in rapid effects compared to other therapeutic agents, makes them a promising class of drugs that may yield effective therapeutics for multiple CNS disorders.
... 50,51 Of particular interest to the subject at hand, ketamine is promising in treating individuals addicted to opioids, alcohol, and cocaine. [52][53][54] CANNABINOIDS Cannabis sativa has been utilized for medicinal, religious, and recreational purposes for over three millennia. It was initially introduced to Western medicine in the 19th century, but its use stagnated due to difficulties obtaining consistent dosages of medical preparations. ...
... As a follow-up to the previous study, the same research team conducted a similar study focusing on the effect of repeated treatments of ketamine-assisted psychotherapy (KPT). 52 This study compared a three-session KPT regimen with a single session in people with heroin addiction. Fiftynine participants were randomly assigned to either a three KPT session group or a control, single KPT session group. ...
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Even as prescription opioid dispensing rates have begun to decrease, the use of illicit opioids such as heroin and fentanyl has increased. Thus, the end of the opioid epidemic is not in sight, and treating patients that are addicted to opioids remains of utmost importance. Currently, the primary pharmacotherapies used to treat opioid addiction over the long term are the opioid antagonist naltrexone, the partial-agonist buprenorphine, and the full agonist methadone. Naloxone is an antagonist used to rapidly reverse opioid overdose. While these treatments are well-established and used regularly, the gravity of the opioid epidemic necessitates that all possible avenues of treatment be explored. Therefore, in this narrative review, we analyze current literature regarding use of the alternative medications ketamine, noribogaine, and cannabinoids in treating patients suffering from opioid use disorder. Beyond its use as an anesthetic, ketamine has been shown to have many applications in several medical specialties. Of particular interest to the subject at hand, ketamine is promising in treating individuals addicted to opioids, alcohol, and cocaine. Therapeutically administered cannabinoids have been proposed for the treatment of multiple illnesses. These include, but are not limited to epilepsy, Parkinson’s disease, multiple sclerosis, chronic pain conditions, anxiety disorders, and addiction. The cannabinoid dronabinol has been seen to have varying effects. High doses appear to reduce withdrawal symptoms but this comes at the expense of increased adverse side effects such as sedation and tachycardia. Noribogaine is a weak MOR antagonist and relatively potent KOR agonist, which may explain the clinical anti-addictive effects. More research should be done to assess the viability of these medications for the treatment of OUD and withdrawal.
... It was approved as an anesthetic in 1970 and is often referred to as a "dissociative psychedelic" [23]. Based on an aversion strategy, ketamine-assisted psychotherapy has been utilized to treat alcoholism and heroin addiction since the 1990s [24]. Research on ketamine has grown in the last 20 years as a treatment option for various psychiatric conditions [25]. ...
... Both the dissociative (2.0 mg/kg) and the non-dissociative (0.2 mg/kg) doses of ketamine reduced opioid craving, promoted longer abstinence, and were associated with positive changes in emotional attitudes [102]. In a follow-up study, repeated treatment sessions were associated with more frequent abstinence a year following treatment [103]. Additionally, administration of a single dose (IV or intranasal) of ketamine following surgical procedures may reduce opioid consumption for pain during recovery [104][105][106][107]. ...
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Purpose of Review This review summarizes recent clinical trial research on pharmacological treatments for substance use disorders, with a specific focus on agents with potential abuse liability. Recent Findings Pharmacological treatments for substance use disorders may include gabapentinoids, baclofen, modafinil, ketamine, cannabinoids, gamma-hydroxybutyrate, and psychedelics. Gabapentinoids may decrease negative subjective effects of withdrawal in alcohol and cannabis use disorders. Cannabinoids similarly appear to decrease use and withdrawal symptoms in cannabis use disorder, while research shows stimulant medications may reduce cravings and increase abstinence in cocaine use disorder. Ketamine and psychedelics may help treat multiple substance use disorders. Ketamine may reduce withdrawal symptoms, promote abstinence, and diminish cravings in alcohol and cocaine use disorders and psychedelics may promote remission, decrease use, and reduce cravings in alcohol and opioid use disorders. Summary Regardless of current regulatory approval statuses and potentials for abuse, multiple agents should not be dismissed prematurely as possible treatments for substance use disorders. However, further clinical research is needed before effective implementation can begin in practice.
... Ketamineassisted therapy (KAT), the treatment approach used in this study, utilized certified behavioral coaches to assist patients in establishing set and setting, and to provide behavioral support in-between medication sessions (more detail is offered below in Procedures-Intervention). Evidence suggests that both exploratory (Krupitsky et al., 2007) and behavioral (Wilkinson et al., 2017) models enhance the effectiveness of ketamine treatment over no behavioral support, but data to date have not determined whether the effectiveness of behavioral intervention is dependent upon therapeutic model or licensure of the provider. Advances in telecommunications have made it less burdensome and more convenient to integrate remote methods of psychosocial care into models of ketamine treatment that emphasize treatment access and safety in a properly selected patient population. ...
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Background At-home Ketamine-assisted therapy (KAT) with psychosocial support and remote monitoring through telehealth platforms addresses access barriers, including the COVID-19 pandemic. Large-scale evaluation of this approach is needed for questions regarding safety and effectiveness for depression and anxiety. Methods In this prospective study, a large outpatient sample received KAT over four weeks through a telehealth provider. Symptoms were assessed using the Patient Health Questionnaire (PHQ-9) for depression, and the Generalized Anxiety Disorder scale (GAD-7) for anxiety. Demographics, adverse events, and patient-reported dissociation were also analyzed. Symptom trajectories were identified using Growth Mixture Modeling, along with outcome predictors. Results A sample of 1247 completed treatment with sufficient data, 62.8 % reported a 50 % or greater improvement on the PHQ-9, d = 1.61, and 62.9 % on the GAD-7, d = 1.56. Remission rates were 32.6 % for PHQ-9 and 31.3 % for GAD-7, with 0.9 % deteriorating on the PHQ-9, and 0.6 % on the GAD-7. Four patients left treatment early due to side effects or clinician disqualification, and two more due to adverse events. Three patient subpopulations emerged, characterized by Improvement (79.3 %), Chronic (11.4 %), and Delayed Improvement (9.3 %) for PHQ-9 and GAD-7. Endorsing side effects at Session 2 was associated with delayed symptom improvement, and Chronic patients were more likely than the other two groups to report dissociation at Session 4. Conclusion At-home KAT response and remission rates indicated rapid and significant antidepressant and anxiolytic effects. Rates were consistent with laboratory- and clinic-administered ketamine treatment. Patient screening and remote monitoring maintained low levels of adverse events. Future research should assess durability of effects.
... A higher rate of abstinence as well as greater and longer-lasting reduction in craving were observed after the first two years of follow-up for the group that received the higher dose of ketamine, which also had greater positive change in nonverbal unconscious emotional attitudes. In a subsequent similar study, Krupitsky et al. [188] compared the effect of a single dose versus repeated sessions of Ketamine-assisted Psychotherapy in detoxified heroin users. All subjects had a ketamine (2.0 mg/kg, im) session prior to their discharge from the hospital and then were randomized into two groups: one received two Addiction Counseling Sessions and ketamine administration one and two months later, while the other had only the two Addiction Counseling Sessions. ...
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Substance use disorder (SUD) is a global public health concern that affects millions of people worldwide. Considering current research, addiction has been noted as the last stage of a chronic disease that may impair brain reward circuit responses and affects personal and social life. Treatments for SUD face challenges including availability and limited pharmacological response, often resulting in low retention of patients. A growing number of studies from the 'psychedelic renaissance' have highlighted the therapeutic potential of psychedelics for several psychiatric disorders, including SUD. In this non-systematic review we discuss past and current clinical and observational studies with classic (LSD, DMT, psilocybin and mescaline) and non-classic (ibogaine, ketamine, MDMA, salvinorin A and THC) psychedelics for the treatment of SUD published until December 2021. Although results are still inconclusive for LSD, DMT, mescaline, MDMA and Salvinorin A, in general, the literature presents moderate evidence on the controlled use of psilocybin and ketamine for Alcohol Use Disorder, ketamine for management of opiate and alcohol withdrawal, and THC preparations for reducing withdrawal symptoms in Cannabis and possibly in Opioid Use Disorder. Importantly, studies suggest that psychedelics should be more effective when employed as an adjunct therapy. Extensive research is warranted to further elucidate the role of psychedelics in the treatment of SUD.
... Ketamine has been investigated as a potential treatment for various substance use disorders. Krupitsky et al. (2007) showed that ketamine assisted psychotherapy is more effective than placebo at promoting abstinence in individuals with heroin addiction. A study by Dakwar et al. (2019) combining a single infusion of ketamine with mindfulness-based therapy showed improved abstinence among individuals with cocaine dependence. ...
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Post-traumatic stress disorder (PTSD), a common condition with potentially devastating individual, family, and societal consequences, is highly associated with substance use disorders (SUDs). The association between PTSD and SUD is complex and may involve adverse childhood experiences (ACEs), historical and multi-generational traumas, and social determinants of health as well as cultural and spiritual contexts. Current psychosocial and pharmacological treatments for PTSD are only modestly effective, and there is a need for more research on therapeutic interventions for co-occurring PTSD and SUD, including whether to provide integrated or sequential treatments. There is a current resurgence of interest in psychedelics as potential treatment augmentation for PTSD and SUDs with an appreciation of the risks in this target population. This paper reviews the historical perspective of psychedelic research and practices, as well as the intersection of historical trauma, ACEs, PTSD, and SUDs through the lens of New Mexico. New Mexico is a state with high populations of Indigenous and Hispanic peoples as well as high rates of trauma, PTSD, and SUDs. Researchers in New Mexico have been leaders in psychedelic research. Future directions for psychedelic researchers to consider are discussed, including the importance of community-based participatory approaches that are more inclusive and respectful of Indigenous and other minority communities.
Background Few studies have evaluated the efficacy of ketamine-assisted psychotherapy (KAP) in the treatment of treatment-resistant depression (TRD) and substance use disorders (SUD). Methods A systematic review of clinical trials reporting on the efficacy of KAP and discussing mechanisms of action, identified on PubMed and PsycInfo. Results Five randomized-controlled trials reported on the efficacy of KAP treatment and discussed active mechanisms. Four of the studies treated adults with SUD and a single study treated adults with TRD. Overall, KAP had a significant positive effect on primary outcome measures compared to controls, however, the data is mixed. The study examining KAP for TRD found no benefit. Limitations Lack of large, replicated clinical trials. No studies actively examining mechanisms of action. Conclusion Evidence suggests that temporary neural changes caused by ketamine such as n-methyl-d-aspartate receptor (NMDAR) inhibition and increase of synaptic neuroplasticity affect treatment outcomes of KAP. Based on reports of preliminary findings, we speculate that adjunct psychotherapy, changes in perspective, and spirituality may also play a role.
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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.
Research into treating drug dependence with hallucinogens, although promising, ended with questions still unanswered because of varying, in some cases skeptical, methodology and insufficient adherence to a double-blind, placebo-controlled design. Interest is again emerging, especially with the recent patenting in the United States of ibogaine for its apparent anti-craving properties. A review of the literature shows that these properties may be present across the entire family of hallucinogens. Potential efficacy may be tied to their agonism and antagonism at specific serotonin receptor sites. After the administration of a hallucinogen, there is a positive “afterglow” lasting weeks to months which might be extended through repeated dosing. Ibogaine and LSD both have lengthy periods of action, making their application unwieldy. However, tryptamines, such as N,N-Dimethyltryptamine (DMT), are so short-acting that they could easily be administered in an office setting. With numerous hallucinogens yet to be tested, a hallucinogen might well be discovered with superior anti-craving properties and non-deleterious side-effect profile.
This study evaluated the dose-related ethanol-like subjective effects of the N-methyl-D-aspartate (NMDA) glutamate receptor antagonist ketamine hydrochloride in recently detoxified alcoholics. Twenty male inpatients meeting DSM-III-R criteria for alcohol dependence and who had not consumed alcohol for 10 to 27 days prior to the study completed 3 test days that involved the intravenous infusion of ketamine hydrochloride (0.1 mg/kg or 0.5 mg/kg) or saline solution under randomized double-blind conditions. Ethanol-like subjective effects were assessed using the Sensation Scale; the Biphasic Alcohol Effects Scale; visual analog scales to measure "high" and degree of similarity to ethanol, cocaine, and marijuana; a scale assessing the number of standard alcohol drinks producing similar subjective effects; and visual analog scales measuring ethanol craving. Ketamine produced dose-related ethanol-like effects on each scale measuring its similarity to ethanol. Its effects were more similar to the sedative or descending limb effects of ethanol than to the stimulant or ascending limb effects. Ketamine effects also were more like ethanol than marijuana or cocaine. Ethanol-like effects were more prominent at the higher ketamine dose, a dose rated as similar to greater levels of ethanol intoxication. However, ketamine did not increase craving for ethanol. The production of ethanol-like subjective effects by ketamine supports the potential clinical importance of NMDA receptor antagonism among the mechanisms underlying the subjective effects of ethanol in humans.
SINCE the initial publications on the development and validation of the Self-Rating Depression Scale (SDS),1,2 there has been continued interest in it. Diversity in the application of this tool is evidenced by its use in the programs of suicide prevention centers, alcoholism clinics, child guidance and adult psychiatric clinics, health and welfare agencies, and by various research groups, including the Veterans Administration Cooperative Studies in Psychiatry and the Early Clinical Drug Evaluation Unit of the Psychopharmacology Research Branch, National Institute of Mental Health. In a series of studies exploring social structure and mental illness, Redlich et al3-6 reported highly significant relationships between social class position and aspects of psychiatric disorders, such as prevalence of psychiatric patients, types of psychiatric disorders, and choice of treatment modalities. If these relationships exist as such, is there a significant correlation between social status and results
Ketamine is a prescription drug used for general anesthesia. In subanesthetic doses, it induces profound psychedelic experiences and hallucinations. The subanesthetic effect of ketamine was the hypothesized therapeutic mechanism in the authors' use of ketamine-assisted psychotherapy for alcoholism. The results of a controlled clinical trial demonstrated a considerable increase in efficacy of the authors' standard alcoholism treatment when supplemented by ketamine psychedelic therapy (KPT). Total abstinence for more than one year was observed in 73 out of 111 (65.8%) alcoholic patients in the KPT group, compared to 24% (24 out of 100 patients) of the conventional treatment control group (p < 0.01). The authors' studies of the underlying psychological mechanisms of KPT have indicated that ketamine-assisted psychedelic therapy of alcoholic patients induces a harmonization of the Minnesota Multiphasic Personality Inventory (MMPI) personality profile, positive transformation of nonverbalized (mostly unconscious) self-concept and emotional attitudes to 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. Most importantly, these psychological changes were shown to favor a sober lifestyle. The data from biochemical investigations showed that pharmacological action of KPT affects both monoaminergic and opioidergic neurotransmitter metabolism, i.e., those neurochemical systems which are involved in the pathogenesis of alcohol dependence. The data from EEG computer-assisted analysis demonstrated that ketamine increases theta activity in cerebrocortical regions of alcoholic patients. This is evidence of the reinforcement of limbic cortex interaction during KPT session.