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Journal of Psychoactive Drugs
ISSN: 0279-1072 (Print) 2159-9777 (Online) Journal homepage: https://www.tandfonline.com/loi/ujpd20
Ketamine Assisted Psychotherapy (KAP): Patient
Demographics, Clinical Data and Outcomes in
Three Large Practices Administering Ketamine
Jennifer Dore, Brent Turnipseed, Shannon Dwyer, Andrea Turnipseed, Julane
Andries, German Ascani, Celeste Monnette, Angela Huidekoper, Nicole
Strauss & Phil Wolfson
To cite this article: Jennifer Dore, Brent Turnipseed, Shannon Dwyer, Andrea Turnipseed,
Julane Andries, German Ascani, Celeste Monnette, Angela Huidekoper, Nicole Strauss & Phil
Wolfson (2019): Ketamine Assisted Psychotherapy (KAP): Patient Demographics, Clinical Data
and Outcomes in Three Large Practices Administering Ketamine with Psychotherapy, Journal of
Psychoactive Drugs, DOI: 10.1080/02791072.2019.1587556
To link to this article: https://doi.org/10.1080/02791072.2019.1587556
© 2019 The Author(s). Published with
license by Taylor & Francis Group, LLC.
Published online: 27 Mar 2019.
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Ketamine Assisted Psychotherapy (KAP): Patient Demographics, Clinical Data
and Outcomes in Three Large Practices Administering Ketamine with
, Brent Turnipseed
, Shannon Dwyer
, Andrea Turnipseed
, Julane Andries
, German Ascani
, Angela Huidekoper
, Nicole Strauss
, and Phil Wolfson
Helios Psychiatry, Woodside, CA;
Roots Behavioral Health, Austin, TX;
Center for Transformational Psychotherapy, San Anselmo, CA;
Ketamine Research Foundation, San Anselmo, CA
Currently, ketamine is the only legal psychedelic medicine available to mental health providers for
the treatment of emotional suffering. Over the past several years, ketamine has come into
psychiatric use as an intervention for treatment resistant depression (TRD), administered intrave-
nously without a psychotherapeutic component. In these settings, ketamine’s psychedelic effects
are viewed as undesirable “side effects.”In contrast, we believe ketamine can benefit patients with
a wide variety of diagnoses when administered with psychotherapy and using its psychedelic
properties without need for intravenous (IV) access. Its proven safety over decades of use makes it
ideal for office and supervised at-home use. The unique experience that ketamine facilitates with
its biological, experiential, and psychological impacts has been tailored to optimize office-based
treatment evolving into a method that we call Ketamine Assisted Psychotherapy (KAP). This article
is the first to explore KAP within an analytical framework examining three distinct practices that
use similar methods. Here, we present demographic and outcome data from 235 patients. Our
findings suggest that KAP is an effective method for decreasing depression and anxiety in
a private practice setting, especially for older patients and those with severe symptom burden.
Received 13 December 2018
Accepted 15 February 2019
The development of a psychotherapy that uses keta-
mine as a medicine for conscious awareness is new and
groundbreaking (Wolfson and Hartelius 2016). It coin-
cides with promising clinical research with psilocybin
and MDMA embedded in psychotherapies that are
entering Phase III FDA trials (Feduccia, Holland, and
Mithoefer 2018; Mithoefer, Grob, and Brewerton 2016).
For now, ketamine is the only legally available psyche-
delic medication, along with cannabis.
Ketamine originated as an anesthetic drug in the late
1960s as an analog of phencyclidine. It has been
a successful anesthetic and analgesic agent with far fewer
adverse effects than the parent compound. Early in keta-
mine’s use, there were reports of an unusual side effect,
a dissociative/hallucinatory state referred to as the “emer-
gence phenomenon.”This was concerning because patients
were not prepared for these vivid experiences and found
them disturbing. It was dubbed a “dissociative anesthetic”
clinician (Matthew and Zarate 2016).
Ketamine’s potential to treat psychological or psychia-
tric problems was first reported in Khorramzadeh and
Lofty (1973), and in Argentina as an adjunct for antide-
pressant psychotherapy (Fontana 1974). In Mexico, the
psychiatrist Salvador Roquet introduced ketamine to
patients in group settings as a component of his approach
to psychedelic psychotherapy (Kolp et al. 2007; Yensen
2016). From Russia came reports of using ketamine for
the treatment of addictions (Krupitsky and Grinenko
1997). Duly noted by those involved with psychedelic
substances during this period prior to the Drug
Enforcement Administration’s scheduling of substances,
use of ketamine for self-exploration and in psychothera-
peutic contexts had an ongoing but not extensive profile
(Jansen 2004; Wolfson and Hartelius 2016).
Anecdotally, some practitioners noted that intramus-
cular ketamine sessions were followed by periods of relief
from depressive and anxious states (Kolp et al. 2007). In
the late 1990s, investigators at the National Institute of
Mental Health began exploring the antidepressant poten-
tial of ketamine while searching for alternatives to the
limited benefits of SSRIs and SNRIs (Berman et al. 2000;
CONTACT Phil Wolfson email@example.com The Ketamine Research Foundation, 6 Crest Avenue San Anselmo, CA 94960
Color versions of one or more of the figures in the article can be found online at www.tandfonline.com/ujpd.
JOURNAL OF PSYCHOACTIVE DRUGS
© 2019 The Author(s). Published with license by Taylor & Francis Group, LLC.
This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License (http://creativecommons.org/licenses/by-nc-
nd/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited, and is not altered, transformed, or built
upon in any way.
Krystal et al. 1994). Notably, however, their effort was
focused on eliminating the psychedelic effects while
retaining or enhancing the antidepressant properties.
They concentrated on patients failing treatment on two
or more conventional antidepressants (labeled Treatment
Resistant Depression [TRD]), viewing this as a potential
market with a social responsibility to provide effective
treatment. Subsequently, a protocol for medicalized use
involving an intravenous (IV) route of administration in
which ketamine was infused at a rate of 0.5 mg/kg over 40
minutes emerged. After a single session of IV ketamine,
investigators noted remission of TRD and a reduction of
suicidality ((Krystal 2007). However, the benefit was
short-lived. This led to a more intensive approach to
providing treatment, tending towards an induction
phase of six sessions over about two weeks' time, with
further sessions occurring at various times depending on
the practitioner. The strategy focused on dosing and
frequency of ketamine administration to extend the dura-
tion of affective benefit (Cusin et al. 2012; Rot et al. 2015;
Zarate et al. 2013).
Although researchers attempted to minimize ketamine’s
unwanted dissociative effects, some degree of mind altera-
tion would generally occur. However, studies from the IV
researchers indicated enhanced benefit from the presence
of psychedelic experiences (Luckenbaugh et al. 2014). These
findings parallel the relationship between mystical experi-
ence and treatment outcome in the psilocybin studies
(Griffiths et al. 2011), with both medicines providing
altered, often profound psychedelic experience. This asso-
ciation suggests that profound psychedelic experiences,
regardless of the medicine facilitating them, may improve
mental health and overall well-being (Sullivan 2018). The
psychiatric establishment has tended to avoid this under-
standing, and instead has attempted to discover
a metabolite or analog of ketamine that lacks the psyche-
delic effects yet retains antidepressant effects. Ketamine
Assisted Psychotherapy (KAP) utilizes a dosage escalation
strategy to achieve different levels of trance increasing to
full out-of-body experiences. We believe that some degree
of mind alteration is necessary for ketamine’seffects.No
study to date has demonstrated that, absent some degree of
perceived psychoactivity, there is an antidepressant effect
(for a review of ketamine research for depression and other
disorders, see Ryan, Marta, and Koek 2016).
In the mid-2000s, several office-based psychiatrists
began administering intramuscular (IM) ketamine within
a psychotherapeutic framework, in collaboration with
referring therapists, or providing therapy themselves
(Early 2016). With Stephen Hyde’s(2015) publication of
Ketamine for Depression in 2015, it became clear that keta-
mine could be administered using the sublingual, intrana-
sal, or intramuscular routes (Chilukuri et al. 2014), raising
the prospect that IV administration was unnecessary. In
fact, other routes of administration allow the entire thera-
peutic dosing spectrum to occur in a non-medicalized office
setting with full psychotherapeutic support (Jaitly 2013;
Over decades, ketamine’srecordofclinicalsafetyin
anesthesia and for analgesia, in emergency room settings,
in outpatient pain management clinics, and now for psy-
chiatric use, has produced an extensive body of clinical
experience that supports its safety (Collins et al. 2010)for
use in the office and for prescription use by patients at
home. We use ketamine both in lower-dose sublingual
administration for a trance experience that promotes inter-
action during the session and the transformational IM
experience with its preparation, journey, and subsequent
For over five years now, KAP has been in clinical
development evolving a set of basic strategies and accu-
mulating experience from several hundred patients and
thousands of KAP sessions. We report here the results of
three distinct KAP practices, each having matured in con-
secutive time frames. Given the evolving nature of KAP,
there is a development of reporting as practices have
settled on particular assessment measures and criteria.
Over time, there has been an increase in available data
and emphasis on patient self-reports. This has enabled the
maturation of a dosing strategy into a replicable protocol.
What is provided here is both a qualitative and quantita-
tive expression and evaluation of our work to date.
The practices reporting here do not limit the use of
KAP to only patients with TRD. KAP has been used for
patients suffering from a variety of problems—relation-
ship and existential issues including post-traumatic stress
disorder (PTSD), Bipolar I and II depressive phases,
obsessive-compulsive disorder (OCD), psychological
reactions to physical illness, personality disorders, life-
threatening illnesses, and substance use co-occurring
with a primary psychiatric disorder. We do not view
ketamine as a stand-alone medicine fitting all possibili-
ties. The encounter here is with practices addressing the
human gamut with all the available tools of psychiatry
Ketamine as a medicine: A brief review
Ketamine is available in two enantiomers: the S (+) and
the R (−) configurations. The S isomer is estimated to
be approximately twice as powerful as the R (Weber
et al. 2004). There is controversy in distinguishing
a pattern of different effects between the two. Current
pharmacological preparations include an equimolar
racemic mixture of the two enantiomers. S (+) keta-
mine has just come to market with FDA approval as
2J. DORE ET AL.
a patented antidepressant nasal preparation for in-
office psychiatric use.
Multiple routes of administration are used by practi-
tioners treating depression and other psychiatric con-
ditions, each with its own unique pharmacokinetics.
These include IV, IM, intranasal (IN), sublingual (SL),
anal, and oral delivery. Each has its own rate of absorp-
tion and timing of onset. In our practices, new patients
tend to begin with the SL method for assessment of
sensitivity to the medicine.
Ketamine’s antidepressant activity is believed to stem
from its antagonism of NMDA receptors within the gluta-
mate neurotransmitter matrix. Based on animal models, it
is believed that ketamine-induced synaptic potentiation
and proliferation may play a key role in eliciting antide-
pressant effects. Ketamine also impacts other neurotrans-
mitter systems, affecting cholinergic, monoaminergic,
kappa opioid, and GABAergic function, most likely as
downstream indirect effects (Wallach 2018). A recent
paper describing the use of naltrexone in six patients receiv-
ing low-dose ketamine infusions (Williams et al. 2018)has
created controversy as to the putative effects of ketamine on
opiod receptors and the possible clinical implications. This
has been contradicted by earlier, more thorough work by
Krystal et al. in 2007; and by receptor research (Wallach
2018). It is our view that the antidepressant effect of keta-
mine is not the direct result of signaling via the opiate
The bioavailability of IM ketamine is similar (93
−95%) to IV ketamine. SL ketamine absorption is vari-
able and difficult to estimate but most likely in the
range of 15–25%. IN ketamine absorption is higher at
about 25–35%, depending on person and preparation.
Oral absorption is much less efficient, at 10% or less,
and takes more time to have its effect (Wieber et al.
1975). The swallowing of ketamine from SL or IN
administration may result in a remote onset of keta-
mine’s effect when it does occur somewhere in the
range of 45–75 minutes later.
Ketamine’s tolerability and safety have been demon-
strated over almost five decades (Jaitly 2013). A pooled
data study from three different clinical trials of subanes-
thetic IV ketamine administration in major depressive dis-
order (MDD) patients found that adverse effects common
within the first four hours of administration included dizzi-
ness, derealization, and drowsiness (McGirr et al. 2014).
Whethertheseareconsidered“adverse”or as part of keta-
mine’s actual effects that result in therapeutic benefit is the
subject of debate. One third of all patients experienced
transient hemodynamic changes, particularly elevated
blood pressure. There have been no cases of persistent
neuropsychiatric sequelae, medical effects, nor increased
substance abuse in clinical practice. Use of a body weight
schema for a determination of ketamine dosage is of limited
clinical utility, as sensitivity to the medicine is idiosyncratic
and only fully predictable with patient experience.
Increasing the dosage of ketamine utilizing any of the routes
of administration will result in an increase in dissociative
The KAP experience: Trance and transformation
KAP’s effectiveness lies in several factors. Depending
upon dose, ketamine promotes a time-out from ordin-
ary, usual mind, relief from negativity, and an openness
to the expansiveness of mind with access to self in the
larger sense. These effects enhance a patient’s ability to
engage in meaningful psychotherapy during and after
administration. Ketamine is potent for respite, analysis,
and meditative presence, and potent for recovery from
depression and the lingering effects of trauma. For
most patients, we begin with the sublingual induction
of the trance state to find an individual “sweet spot”
with respect to dosage that can be replicated at home
under supervision and used in future in office sessions
to aid in psychotherapy. We may then move to the IM
experience of transformation based on the patient, pro-
ducing an out-of-body experience which allows for
a unique but related approach to healing. These two
modes of treatment are outlined in Table 1.
KAP is intensive, demanding, and rewarding for its
practitioners and their patients. The long sessions, up to
three hours, plus provision of supervised recovery for
patients, can be fatiguing. As with any mind-altering
experience, there are set and setting considerations. In
our offices, we make every effort to provide a nest in the
Winnicott sense, a place of safety and warmth (Carhart-
Harris et al. 2018). Since the breakage of trust or the lack of
its acquisition are so much at the core of trauma persis-
tence, the behavior of therapists and their ability to bond
with patients are at the heart of our psychotherapy (Van
Der Kolk 2014). Long exposure to each other requires
a more human, intimate, and disclosing posture by thera-
pists while maintaining the boundary of “not needing”of
our patients. Attachment wounds are best healed in
a therapeutic environment that is reliable, compassionate,
appears safe, and recognizes the vulnerability of its patients
(Brown and Elliott 2016). An altered state is a vulnerable
state. In recognition of this, we frequently work dyadically,
enabling our patients to let down vigilance and journey
freely and without concern for intrusion or violation. If two
therapists (including an MD, FNP, or NP) are not available,
we have another therapist present on premises. This prac-
tice is in accord with the method of MAPS MDMA-
assisted psychotherapy. Adaptation of different methods
to psychedelic psychotherapy, such as Internal Family
JOURNAL OF PSYCHOACTIVE DRUGS 3
Systems (Schwartz 1995), is an opportunity for growth and
creativity and for expansion of the theory and practice of
Maintenance of the observing self is fundamental to
the success of our work and guides dosage selections.
Our monitoring consciousness rides with the journey
and comments at a fundamental level. It is accentu-
ated and deepened as in profound meditative states.
The journey tends to augment meditative ability and
stability (Millière et al. 2018).
Table 2 highlights the “signature”of the ketamine
experience and therapeutic integrations.
In the freedom of an inward journey, absent the
emotional constraints of ordinary mind and free of
one’s sense of inherent form, a sense of vast space arises.
The journey unfolds in different realities that may seem
the truth of being, outside of time and space, as if
observing our being in different realities. At times, this
may be confusing as the experience may be intense with
only the observing mind connecting to a sense of self.
This study is of KAP’s effectiveness in providing the
means to personal elucidation which results in decrease
in symptomatology. We call this anchoring the essential
elements gained from the experience. This can take
many forms, including slogans, mantras, visions, inter-
nal movies, feelings, metaphors, and understandings.
This is about learning from the experience, bringing it
Table 1. The KAP experience: Trance and transformation.
Trance State –SL with dose ranges
25–400 mg varying with
individual–slower onset 8–20 min
Promotes communication, access
to difficult states of mind with less
fear of those encounters, and
a relief from obsessive and
depressive concerns. Conscious
awareness and an ability to
communicate with attending
and involved relatives is
maintained throughout the
experience, often with a reduction
in direct verbal output. Integrate
a sense of newness and healing,
this occurring as the main
experience diminishes. Working
with this state is usually a multiple-
session process that can last
anywhere from two weeks to many
Transformational State –IM
with dose ranges of 25–130 mg
varying with the individual–fast
onset 2–4 min, patients with less
sensitivity may receive higher
Reduction of body and sensory
awareness of an ego reductive,
spiritual and liberatory nature—
from our usual sense of our
constitution. While the full out-of-
body experience is primarily
reached with an IM injection, it
may also be accessed with the
sublingual lozenge, depending on
individual sensitivity and dose.
With diminution of tactile and
visual sensation, and alteration of
auditory receptivity, the internal
visual realm is activated. Verbal,
intellectual description is limited.
Note: In our practices, we use the first KAP session to determine an
individual patient’s dose response curve and thus their individual dose
range that will allow them to reliably access the trance state in office
sessions and at home. The trance state is ideal for psychotherapy and
meditative self-reflection. The deep or peak experience tends to last
25–60 minutes with a period of lesser intensity following, usually lasting
less than an hour. Set and setting and the presence of skilled therapists in
the KAP process make for integrations of powerful experiences that are
healing and rectifying. The role of the therapist is to support the indivi-
dual to find their own path, their own peace–or wrath, their own
accommodation and acceptance of the life lived—or not. KAP is an
experience of self that is mediated by contact with administering thera-
pists and attendant loved ones, but without imposition of values and
Table 2. The ketamine signature.
Psychopharmacology Rapid onset
Dosage escalation enables, then reduces,
Dose-related reduction or elimination of external
sensations, particularly visual, tactile, and auditory
Effects Sensual–as connectedness and appreciation.
Physically sensually stimulating for some. Recall
may be limited and is dose-dependent.
Observing self present throughout, independent of
recollection. Awareness consciousness heightened.
Fluid connectivity and thematic movement =
unique experiences. The mind roams freely while
Little ability to direct the experience.
Heightened internal visual experience; reduction
of verbal thinking. Entering a different reality–total
at higher doses; can be confusing. Transition to
a state separate from obsessions, circularity, and
Qualia Out-of-body experience; out of bounded time; out
of bounded space. Ego dissolution.
Humility–as situating one’s self in time and space–
a larger view of one’s smallness. Cosmic
Love as connectedness. Formlessness.
Experience of being an energy format.
Apprehension of death from the perspective of
Spacious Presence Absence of negative emotions. A peaceful
Effortless self-acceptance. Possibility for highly
positive affect. Self-appreciation.
Breakage of patterns and circularity.
Perception of the depressive door opening to new
experience. Remodeling of sense of self.
Enhanced flexibility. Discrimination of wisdom.
Trust in the stability of the mind. Discrimination of
Putting trauma in the past. Moving towards
A relaxation of habitual vigilance and distrust of
self. A tendency to accept impermanence.
Reduction of negativity.
Enhanced capacity for meditative mindfulness.
New mental formations.
Respect for mental capacities. Diminution in the
fear of going crazy. Awe.
Ego dissolution, opening the mind to
wonderment. Reduction of negative narcissism
and self-obsession. Trust in self and others.
Sense of spaciousness and capaciousness of mind.
Trust in the intuitive self and spontaneity.
Relaxation and openness to experience and to
4J. DORE ET AL.
as method to everyday life. In essence, we use the
experiential component of the medicine to bring new
perspective and the direct experience of seeing our-
selves in a new way—the missing link that gives hope
to many sufferers of mental illness and others who
cannot achieve this critical reframing by other means.
All participants provided written informed consent.
Three forms were developed for data collection by the
Ketamine Research Foundation (KRF) Ketamine Data
Project (KDP) using a Redcap research database:
Intake, Visit, and Termination (when applicable).
Chart data were inputted consecutively from all three
practices. Where charts were incomplete, or the work
was too limited to input, a list of these was generated
with rationales for exclusion.
The forms contain demographic, diagnostic, medica-
tion, psychoactive history, psychiatric history, medical
history, and family data. Rater views of personality
rigidity, recommendations for ketamine administra-
tion, and concerns are included in the intake form. Self-
report data collected before KAP treatment (baseline/
intake) included the Beck Depression Inventory (BDI),
Hamilton Anxiety Scale (HAM-A), Patient Health
Questionnaire–9 (PHQ-9), Childhood Resilience Scale
(CRS), and Adverse Childhood Event Score (ACE).
Follow-up self-report measures from the last
available office visit included BDI, HAM-A, PHQ-9,
and Levine Depression Scale Ratings. Rater view of
patient’s symptoms as well as the quality of the KAP
session experience were recorded. Change of State,
Mystical Experience Questionnaire (MEQ), and Ego
Dissolution Index (EDI) (Nour et al. 2016) were used
to assess KAP sessions.
During KAP treatment, patients received ketamine SL,
IM, or both during their treatment course. SL ketamine
was administered as either troche or a rapid-dissolve
tablet during the initial in-office session to determine
sensitivity and dose for the individual. Dose ranges were
titrated in office and then adjusted at home to achieve and
maintain access to the trance state described. This state
facilitates psychotherapy sessions and individual reflec-
tion at hometo maintain the therapeutic momentum, and
cannot be determined by a weight-based protocol in our
experience. Subsequently, SL ketamine was prescribed in
a limited amount without refills for at-home use with
instructions to use SL ketamine up to but not exceeding
six sessions over a two-week period, with less frequency
thereafter, depending on severity. Patients were instructed
to replicate the setting and procedure demonstrated by
the clinicians in the initial session at home. KAP sessions
were generally held in the office usually two weeks apart,
or more frequently depending on acuity. Different diag-
noses have different frequencies for KAP and all of our
practices are individualized. IM ketamine was adminis-
tered during in-office sessions only, usually supported by
ongoing SLsessions at home. IM doses were used to reach
the transformational state described earlier in which out-
of-body experiences are common and therapeutic. Not all
patients moved on to use the IM route of administration,
and this was determined at the discretion of the provider
based on therapeutic progress and symptom relief.
Rater views of KAP effects proceed through the Visit
and Termination forms, as does the history of admin-
istration. Raters provide their estimates of the presence
and intensity of psychedelic effects and their impacts,
sensitivity to ketamine, changes in symptoms and well-
being, plus adverse effects, drug interactions, changes in
medications, changes in diagnosis, and commentary of
a psychodynamic and qualitative nature.
SAS software was used to analyze the data. Statistical
tests used include correlations and moderation ana-
lyses. P-values were recorded and reviewed for clinical
relevance by the authors.
Data from 235 patients from three distinct private
general psychiatric practices located in Northern
California (Wolfson and Dore) and Austin, Texas
(Turnipseed) from 2013–2018 were collected prospec-
tively and analyzed retrospectively. Diagnoses among
these KAP patients at intake are shown in Figure 1.
Frequency of Adverse Effects is shown in Figure 2.
The sample had a mean age of 42.7 years, 48.9% were
women, and 85.5% had either a bachelor’sdegreeor
postgraduate degree. Patient’s initiating KAP treatment
were taking an average of 2.84 medications for psychiatric
complaints at intake. These included antidepressants, sti-
mulants, mood stabilizers, antipsychotics, sedatives/
anxiolytics, and other medications. On average, indivi-
duals fell in the moderate depression category as per BDI
(mean = 26.55) and moderate anxiety category as per
HAM-A scale (mean = 20.35) before treatment and had
a significant ACE score (mean = 3.63). Average resilience
score at baseline was 8.27. About one-third (35%) of our
population had previous experience with psychoactive
substances. These included MDMA (n=34),LSD(n=
34), psilocybin (n= 29), ayahuasca (n=6),andketamine
(n= 6). Usual number of years in psychotherapy for our
KAP patients was 3–5 years. Total number of people who
received IM ketamine was 61.5%. The average dose range
of ketamine during KAP sessions was 200–250 mg for the
SL route and 80–90 mg for the IM route in our sample.
JOURNAL OF PSYCHOACTIVE DRUGS 5
Outcomes included decreases in anxiety and depres-
sion. Figure 3 demonstrates clinically significant
improvements in depression and anxiety as measured
by BDI and HAM-A. Subset analysis of the improve-
ment in depression and anxiety demonstrates that
patients with developmental trauma (cPTSD) or devel-
opmental trauma have greatest improvement in depres-
sion and anxiety scores. Patient self-reported measures
(HAM-A, BDI, change of state scores) correlated with
clinician rater views on visit and termination forms
(including depression, anxiety, PTSD, well-being), con-
firming internal consistency between clinician report
and patient self-report. Pvalues for all of these correla-
tions were significant at p< 0.0001.
Number of in-office KAP sessions ranged from 1 to
25 sessions, which were spread over variable time peri-
ods from initial session to visit evaluation to termination
where applicable. The number of ketamine sessions posi-
tively correlated with improvements in the Levine Rapid
Depression Scale (p<0.001),andimprovementsinBDI
from pre- to post-treatment (p< 0.01), indicating that
a higher number of visits was correlated with greater
improvements in depression post-treatment. Treatment
duration positively correlated with Depression Rater
View (p< 0.05) and Anxiety Rater View (p<0.05),
showing that those with a longer total duration of treat-
ment also showed greater improvements in depression
Figure 1. Distribution of most common diagnoses in our sample population. At intake, patients underwent a full psychiatric
evaluation by licensed mental health providers (MD/NP/therapist teams) who assessed whether patients meet diagnostic criteria
according to the DSM-V. Diagnosis are listed: Major Depressive Disorder (MDD), Developmental Trauma (cPTSD), Attention Deficit
Hyperactivity Disorder (ADHD), Post Traumatic Stress Disorder (PTSD), Generalized Anxiety Disorder (GAD), Substance Use Disorder
(SUD including Alcohol n= 14, Cannabis n= 11, Opioid n= 3, Inhalant n= 3, Cocaine n= 1, Nicotine n= 1, Stimulant n= 1, and
Other psychoactive n= 5), Other anxiety disorder (Unspecified, Due to physiological cause, SAD, Agoraphobia, Panic), Other mood
disorder (Bipolar Disorder, Unspecified, Premenstrual Dysphoric Disorder, Dysthymia).
Figure 2. The most common side effects seen in our KAP population are nausea, vomiting, and agitation, which occur only in a small
percentage of patients undergoing KAP treatment and rarely lead to discontinuation of the treatment.
6J. DORE ET AL.
Patients with severe symptom burden (including
higher BDI at intake, suicidality at intake and within
past year, history of psychiatric hospitalization, and
higher ACE scores) had more significant improvements
with KAP treatment, as demonstrated by greater
improvement in anxiety scores, well-being scores, BDI,
PTSD scores, drug and alcohol use scores with treatment,
p< .01 for all correlations. Additionally, increased age was
correlated with greater improvement of depression as per
rater view (p< .05), lower HAM-A with treatment (p<
.01), and lower BDI with treatment p< .05.
KAP is a unique, ground-breaking treatment with two
essential modalities that have led to successful treatment
outcomes in our clinical practices. We have presented
these two modalities as “trance”and “transformation.”
Ketamine has a dose-related continuum of psychoactivity
that modifies therapeutic communication and interac-
tion, and which provides a range of effects from one
medicine decreasing symptoms and facilitating new
ways of being for our patients. Our view is that the
psychedelic, or dissociative, effects are an integral part of
KAP, not to be feared or avoided, but instead that offer
benefit to our patients when supported and integrated in
a psychotherapeutic context. This benefit occurs not only
across a range of doses but also for a range of diagnoses
and human difficulties that present within the context of
a general psychiatry private practice. KAP stands at the
forefront of legal psychedelic psychotherapies as MDMA
and psilocybin enter Phase 3 Studies. The practice of KAP
has thus laid the groundwork for a growing body of
practitioners who will adopt the principles of psychedelic
psychotherapy as a part of the future of mental health
In this study, we present a portrait of KAP which
combines patient experiences from three practices of
different maturity. Importantly, we found significant
benefits for many diagnoses. The population we present
reflects the interest from the general population in
ketamine work, often stemming from failed prior treat-
ments. Our patients come to KAP with moderate levels
of depression and anxiety, and a significant amount of
adverse childhood events.
given that the most common reason for discontinuing
conventional pharmacological treatment for depres-
sion and anxiety is the inability to tolerate side effects
such as nausea or sexual dysfunction. Ketamine can be
administered frequently when symptoms are acute (up
to every 48 hours), or periodically in a maintenance
format, depending on the needs of the patient.
Episodic, intermittent use of a medication is, for
many patients, preferable to constant exposure, as
with daily antidepressants. Intermittent use of medi-
cation also decreases the potential for adverse effects.
We also note that, despite the stigma of recreational
use and concerns regarding addiction, ketamine used
in KAP practice does not produce any physical depen-
dence. Importantly, we have not had patients seek
ketamine outside of our clinical practices or encoun-
tered any other indication of addictive behavior.
Figure 3. Average BDI and HAM-A scores at baseline compared with follow-up reveal a statistically significant decrease in anxiety
and depression with treatment. Intake BDI scores on average fell in the range of moderate depression (20–28) and decreased an
average of 11.24 points to mild depression range. Intake HAM-A scores fell in the moderate anxiety category and decreased on
average 5.5 points to the mild anxiety category.
JOURNAL OF PSYCHOACTIVE DRUGS 7
Despite the fact that much of our cohort was naive
to psychoactive experiences (65% naive to psychoac-
tives), patients were open to their future ketamine
experiences having psychedelic aspects. Psychedelic
experiences were well-tolerated and sought after as an
essential component of their healing process. Our
patient population, in their at-home administration,
under close supervision, adjusted their dosage to
a balance between trance depth and recollection of
their experiences. This aspect of our work is unique
in that it requires patients to be more engaged and
creative in their own settings.
Our patients experienced a clinically significant decrease
in anxiety and depression with treatment as compared to
baseline at intake. We also found that patients who have
more severe symptoms, including current suicidality, high
BDI at intake, and higher ACE score, tend to show the
most significant benefit. These correlations help us to begin
to form hypotheses about which types of patients benefit
most from KAP and will help guide treatment decisions
and the integration of this modality into general psychiatric
practice. Findings are limited by the instruments we have
used to measure change. In our clinical experience, we have
observed significant benefit even in the patients who
appear to function relatively well and report less sympto-
matology. Future studies are needed to characterize these
Ketamine is not for everyone. Some patients are
sickened by ketamine and a subset (< 5%) cannot
tolerate the nausea and vomiting experienced even
with preventative medication. A small percentage
(1–2%) do not respond to ketamine even at high IM
doses. Others, particularly those with rigid personality
structures, such as those with severe OCD or person-
ality disorders and perhaps severe PTSD, find entering
the trance state difficult and are not able to sustain the
benefits they experience during the actual sessions,
even if they do indeed experience some relief.
While we are unable to comment on neurobiological
mechanisms of action, there is the suggestion that neu-
roplastic changes may be at work, as well as possible
anti-inflammatory effects. Our finding that older
patients have more significant improvement in depres-
sion over the course of their treatment tends to support
this. We thought at first that increased benefit with age
might reflect the amount of psychotherapy that
a patient had upon entering KAP treatment; however,
this variable was not significant.
KAP differentiates itself from the IV practices that have
burgeoned in recent years. We have presented our office-
based practices and our controlled prescriptions for at-
home use. While we follow the protocol that includes
frequent sessions in the first stage of ketamine’sapplication
for depression and TRD (most commonly six sessions in
two weeks, which may be repeated until remission is
achieved), our work embeds ketamine administration
within a psychotherapeutic framework for both in-office
sessions and home use. As therapy proceeds, we move to a
maintenance approach with less frequent ketamine ses-
sions, or sessions that are conducted to prevent significant
relapes. We provide treatment plans that include varied
frequencies and doses of administration for other psychia-
tric diagnoses, adapting our KAP treatment to each
patient’s individual needs through frequent contacts and
Comparison of outcomes and effects between the IV
practices and KAP are difficult to obtain at this point.
Our data set appears to be more complex than what is
reported by the IV practices and we have the benefit of
experience in diagnosing and treating psychiatric dis-
orders and combining treatment modalities. We antici-
pate showing a more complete set of our emerging data
in the next year as uniformity in reporting enables this.
Presently, the use of ketamine with KAP versus the IV
practices differentiate in methodology, as well as in
economics. KAP, even with its intensity and long ses-
sions, is significantly less expensive overall.
Table 1 describes our approach for achieving both the
Trance and Transformation experiences in individual
patients, this method having been developed over the five
years that KAP has been practiced. Thus, our positive
findings in this article reflect an evolving methodology
using ketamine with psychotherapy as described, as
opposed to a specific protocol. We have now developed
a step-by-step approach that is manualized and taught in
our trainings (In trainings conducted by KRF). Further
research is required to refine, validate, and test the compo-
nents of this protocol, and to compare outcomes of the
protocol with those of IV ketamine interventions and with
standard of care interventions in mental health treatment.
In addition, affordability and access to treatment are
a major concern for both practitioners and potential
Ketamine Assisted Psychotherapy is a new and unique
methodology with a rapidly growing group of practi-
tioners participating in its development and practice.
We have presented a view of its current status combining
data from three different related centers, with
attendant outcomes with correlations. Psychedelic experi-
ence is an inherent, valued, and well-tolerated part of our
methodology. Our data support the efficacy of KAP for
a wide variety of psychiatric diagnoses and human
8J. DORE ET AL.
difficulties, significantly diminishing depression, anxiety,
and PTSD and increasing well-being.
None of the authors of this paper have a financial interest or
benefit arising from the direct applications of this research.
Brown, D. A., and D. Elliott. 2016.Attachment disorder in
adults. New York, NY: W.W.Norton.
Carhart-Harris, R., L. Roseman, E. Haijen, D. Erritzoe, R. Watts,
I. Branchi, and M. Kaelen. 2018, July. Psychedelics and the
essential importance of context. Journal of
Psychopharmacology 32 (7):725–31. Epub 2018 Feb 15.
A. Shaik. 2014. Acute antidepressant effects of intramuscular
versus intravenous ketamine. Indian Journal of Psychological
Medicine (36/1):71–76. doi:10.4103/0253-7176.127258.
Collins, K., J. Murrough, A. Perez, D. Reich, D. Charney, and
S. Mathew. 2010. Safety and efficacy of repeated-dose intrave-
nous ketamine for treatment-resistant depression. Biological
Psychiatry 67 (2):139–45. doi:10.1016/j.biopsych.2009.08.038.
Cusin, C., G. Hilton, A. Nierenberg, and M. Fava. 2012.Long-
term maintenance with intramuscular ketamine for
treatment-resistant bipolar II depression. American Journal
of Psychiatry 169:868–69. doi:10.1176/appi.ajp.2012.12020219.
Early, T. 2016. Making ketamine work in the long run. In The
ketamine papers: Science,therapy and transformation, ed.
P. Wolfson and G. Hartellius, 305–22. Santa Cruz, CA:
and promise for the MDMA drug development program.
Psychopharmacology 235 (2):561–71. doi:10.1007/s00213-017-
Fontana, A. 1974. Terapia atidepresiva con ketamine. Acta
psiquiatrica y psicologica de America latina 20:32.
Griffiths, R., M. Johnson, W. Richards, B. Richards,
U. McCann, and R. Jesse. 2011. Psilocybin occasioned
mystical-type experiences: Immediate and persisting
dose-related effects. Psychopharmacology (Berl) 218
Hyde, S. J. 2015.Ketamine and depression. Tasmania: Xlibris.
Jaitly, V. 2013.Sublingual ketamine in chronic pain: Service
evaluation by examining more than 200 patient years of
data. Journal of Observational Pain Medicine 1/2 (2013).
Jansen, K. 2004.Ketamine: Dreams and realities. Santa Cruz,
Khorramzadeh, E., and A. Lofty. 1973. The use of ketamine
in psychiatry. Psychosomatics 14:344–46. doi:10.1016/
L. O’Connor. 2007. Ketamine-enhanced psychotherapy:
Preliminary clinical observations on its effects in treating
death anxiety. International Journal of Transpersonal Studies
Krupitsky, E., and A. Grinenko. 1997. Ketamine psychedelic
therapy (KPT)—A review of the results of ten years of
research. Journal of Psychoactive Drugs 29 (2):165–83.
Krystal, J. H. 2007. Ketamine and the potential role for
rapid-acting antidepressant medications. Swiss Medical
Weekly 137 (15–16):215–16.
Krystal, J. H., L. P. Karper, J. P. Seibyl, G. K. Freeman,
R. Delaney, J. D. Bremner, and D. S. Charney. 1994.
Subanesthetic effects of the noncompetitive NMDA
antagonist, ketamine, in humans: Psychotomimetic, per-
ceptual, cognitive, and neuroendocrine responses. Archives
of General Psychiatry 51 (3):199–214. doi:10.1001/
Krystal, J. H., S. Madonick, E. Perry, R. Gueorguieva,
L. Brush, Y. Wray, A. Belger, and D. C. D’Souza. 2006.
Potentiation of low dose ketamine effects by naltrexone:
Potential implications for the pharmacotherapy of
alcoholism. Neuropsychopharmacology 31 (8):1793–800.
Lara, D., L. Bisol, and L. Munari. 2013. Antidepressant, mood
stabilizing and procognitive effects of very low dose sublingual
ketamine in refractory unipolar and bipolar depression. The
International Journal of Neuropsychopharmacology 16
Luckenbaugh, D. A., M. J. Niciu, D. F. Ionescu, N. M. Nolan,
E. M. Richards, N. E. Brutsche, and C. Zarate. 2014. Do the
dissociative side effects of ketamine mediate antidepressant
effects. Journal of Affective Disorders 159:56–61.
Matthew, S., and C. Zarate, editors. 2016.Ketamine for
Treatment Resistant Depression. Switzerl: Adis, Springer
R. W. Lam. 2014. A systematic review and meta-analysis of
randomized, double-blind, placebo-controlled trials of keta-
mine in the rapid treatment of major depressive episodes.
Psychological Medicine. doi:10.1017/S0033291714001603.
Millière, R., R. Carhart-Harris, L. Roseman, F. Trautwein,
and A. Berkovich-Ohana. 2018, September 4.
Psychedelics, meditation, and self-consciousness. Frontiers
in Psychology 9:1475. doi: 10.3389/fpsyg.2018.01475.
Mithoefer, M. C., C. S. Grob, and T. D. Brewerton. 2016.
Novel psychopharmacological therapies for psychiatric dis-
orders: Psilocybin and MDMA. The Lancet Psychiatry 3
(5):481–88.Epub 2016 Apr 5. doi:10.1016/S2215-0366(15)
Nour, M. M., L. Evans, D. Nutt, and R. L. Carhart-Harris.
2016, June 14. Ego-dissolution and psychedelics:
Validation of the Ego-Dissolution Inventory (EDI).
Frontiers in Human Neuroscience 10:269. doi: 10.3389/
R. M.A. Cappiello, A. Anand, D. Oren, G. Heninger,
D. Charney, and J. Krystal. 2000. Antidepressant effects
of ketamine in depressed patients. Biological Psychiatry 47
Rot, M., K. Collins, J. Murrough, A. Perez, D. Reich, D. Charney,
and S. Mathew. 2015. Safety and efficacy of repeated-dose
intravenous ketamine for treatment-resistant depression.
Biological Psychiatry 67/2:139–45. doi:10.1016/j.biopsych.
JOURNAL OF PSYCHOACTIVE DRUGS 9
Ryan, W., C. Marta, and R. Koek. 2016. Ketamine and
depression: A review. In The ketamine papers, ed.
P. Wolfson and G. Hartellius, 199–273. Santa Cruz, CA:
Schwartz, R. 1995.Internal family systems therapy. New York,
NY: The Guilford Press.
Sullivan, P. 2018. Using ketamine to treat addictions. Paper
presented at the Kriya Conference, The Nueva School.
Hillsborough, CA, November 4.
Van Der Kolk, B. 2014.The body keeps the score. London,
UK: The Penguin Group.
Wallach, J. 2018. Pharmacokinetics and pharmacodynamics
of ketamine (and Related Compounds). Paper Presented at
the Kriya Conference, The Nueva School. Hillsborough,
CA, November 2.
Weber, F., H. Wulf, M. Gruber, and R. Biallas. 2004.S-
ketamine and s-norketamine plasmaconcentrations after
nasal and iv administration in anesthetized children.
Paediatr†anaesth 14 (12):983–988.
Wieber, J., R. Gugle, J. Hengstmann, and H. Dengler. 1975.
Pharmacokinetics of ketamine in man. Anaesthesist 24
Williams, N. R., B. D. Heifets, C. Blasey, K. Sudheimer, J.
Pannu, H. Pankow, J. Hawkins, J. Birnbaum, D. M. Lyons,
C. I. Rodriguez, and A. F. Schatzberg. 2018. Attenuation of
antidepressant effects of ketamine by opioid receptor
antagonism. The American Journal of Psychiatry 175
Wolfson, P., and G. Hartelius, editors. 2016.The ketamine
papers. Santa Cruz, CA: MAPS.
Yensen, R. 2016. Psychedelic experiential psychology:
Pioneering clinical explorations with salvador roquet. In
The ketamine papers, ed. P. Wolfson and G. Hartellius,
69–93. Santa Cruz, CA: MAPS.
Zarate, C., R. Duman, G. Liu, S. Sartori, J. Quiroz, and
H. Murck. 2013. New paradigms for treatment-resistant
depression. Annals of the New York Academy of Sciences
1292 (1):21–31. doi:10.1111/nyas.12223.
10 J. DORE ET AL.