A Blueprint for Implementing Ketamine-Assisted Psychotherapy in Palliative Care: Design, Process, and Treatment Patterns of a Real-World Clinical Program

Abstract

Background:

Psychospiritual distress (PSD) causes profound suffering in people with serious illness, yet treatment options are few and evidence of their efficacy is modest. Although high-level evidence is limited, decades of preliminary research suggest that psychedelic-assisted psychotherapy (PAP), including ketamine-assisted psychotherapy (KAP), may alleviate the anxiety, depression, and existential distress associated with PSD. However, clinical examples and published implementation frameworks for integrating these interventions into palliative care are scarce. To help bridge this gap, we describe the development and delivery of a palliative care-embedded KAP program at an academic medical center.

Objective:

To describe the design, implementation, and clinical experience of Pal-KAP, a safety-centered and equitably accessible KAP program embedded in outpatient palliative care.

Methods:

We detail the program’s origins, team composition and training, operational model, patient selection and consent process, session structure, safety protocols, and financial model. We summarize patient characteristics and treatment patterns and share illustrative clinical vignettes from the program’s first 28 months.

Results:

Between May 2023 and September 2025, 59 patients were referred for Pal-KAP screening; 43 met the eligibility criteria, and 30 elected to participate. Patients (age 19–76, mean 53) completed a median of 1.5 medicine sessions (range 1–5). Most had cancer (80%) or neurological disease (13.3%). Ketamine dose averaged 0.93 mg/kg intramuscularly, with minor adverse effects (anxiety, headache, nausea, insomnia, dizziness) and no serious adverse events.

Conclusion:

To our knowledge, this is the largest published cohort of KAP in an academic palliative care context. Our Pal-KAP experience suggests that KAP can be delivered safely and ethically, providing a practical blueprint for programs exploring innovative ways to address PSD.

Introduction

Psychospiritual distress (PSD) is the multidimensional experience of illness-related psychological and spiritual pain that causes profound suffering in people with serious illness. It encompasses symptoms of depression, anxiety, demoralization, anticipatory grief, loss of meaning, and existential despair, each affecting up to 60% of seriously ill patients.^1-15 Despite PSD’s prevalence and impact, treatment options are few, and evidence supporting their efficacy is modest, particularly in patients with advanced disease.^16-23

Psychedelic-assisted psychotherapy (PAP)—the combination of psychedelic compounds and psychotherapeutic support—shows growing promise in this context.^24-36 Like the so-called “classical” serotonergic psychedelics such as psilocybin and lysergic acid diethylamide (LSD), the NMDA antagonist ketamine at subanesthetic doses also reliably induces a nonordinary state of consciousness (NOSC). When paired with psychotherapy, NOSCs may benefit seriously ill patients experiencing PSD.^34,35,37-39 They have been shown to reduce psychological rigidity,^40-43 lessen the emotional charge of traumatic memories,^44-49 and diminish the fear of death.^50,51 When explored and integrated within a strong therapeutic alliance,^52,53 the associated experiences and insights can foster affirmation, exploration, acceptance, and the development of practices to support ongoing growth.^54-56 Ketamine-assisted psychotherapy (KAP), PAP using ketamine as the psychedelic, aligns with palliative care’s longstanding practice of using off-label treatments for challenging symptoms when supported by evolving evidence,⁵⁷ including the well-established use of ketamine for pain, here applied to PSD.^38,58-61

Yet, despite increasing interest and preliminary efficacy data on integrating psychedelics into palliative care,^62-70 clinical examples and published implementation frameworks remain scarce. This article aims to bridge that gap by offering a detailed account of the design and delivery of Pal-KAP, an interdisciplinary, equitably accessible, safety-centered KAP program integrated within palliative care.

We describe the program’s origins, rationale, and design; clinical workflow and safety infrastructure; and patient profiles, treatment patterns, and emerging clinical experience from the program’s first 28 months, including three clinical vignettes. We also present 10 pillars for program development to guide clinicians seeking to responsibly integrate KAP into their own palliative care settings and researchers seeking to study KAP models of care.

Origins, Rationale, and Program Design

From concept to clinic: building Pal-KAP

After two years of strategic planning, stakeholder engagement, and institutional groundwork, Pal-KAP was launched at the University of Rochester Medical Center (URMC) in May 2023 with patient screening, followed by the first patient visit in June 2023. Cocreated by a physician (R.K.H.) and a psychologist (M.T.S.) trained in PAP and KAP, the program was developed in close collaboration with an interdisciplinary team of physicians, nurses, social workers, pharmacists, and administrators. From its inception, several key factors shaped Pal-KAP’s development:

• Interdisciplinary foundation: Input from the departments of medicine, psychiatry, nursing, anesthesiology, pharmacy, and advancement ensured alignment of clinical, operational, and regulatory priorities.

• Palliative care integration: Pal-KAP was embedded within URMC’s palliative care clinic as a natural, creative extension of the specialty’s holistic, patient-centered approach to enhancing well-being.

• Research-informed design: Participation in a parallel multisite KAP clinical trial (NCT05214417) prompted early engagement with regulatory frameworks, secured institutional support, and although the trial closed due to recruitment challenges, provided initial momentum and valuable organizational learning.

Supported by institutional administration, Pal-KAP’s first year of implementation provided ongoing observations of feasibility and acceptability, alongside patient and referring clinician feedback, which informed iterative program refinement. One year after program initiation, Pal-KAP received formal approval from a multidisciplinary institutional clinical advisory body, affirming its alignment with clinical and ethical standards and granting it broader institutional recognition.

Why ketamine-assisted psychotherapy?

Ketamine, approved by the FDA as an anesthetic in 1970 and widely used in palliative care, offers a combination of clinical and operational advantages that make it particularly suitable for PAP in people with serious illness (Box 1):

Box 1. Rationale for Ketamine-Assisted Psychotherapy in Palliative Care.

1. Accessibility

   Ketamine is legally available and on hospital and clinic formularies unlike investigational schedule 1 psychedelics.

2. Clinical familiarity

   Palliative care teams often have substantial experience with ketamine’s off-label use and safety,^58,71 supporting broad, confident, and ready implementation.

3. Palliative signature

   More reliably than other psychedelics, ketamine induces NOSCs including experiences of disembodiment or death-like perceptions,^72,73 which are therapeutically relevant for many palliative care patients with PSD.

4. Time-efficient dosing

   Ketamine’s shorter NOSC (typically under one hour) compared with other psychedelics makes sessions more manageable for seriously ill patients, integrates more easily into clinical schedules, and expands program capacity.

5. Cost and access

   Generic racemic ketamine is inexpensive and easily subsidized, supporting wider patent access than emerging psychedelic medications.⁷⁴

6. Medication compatibility

   Ketamine can be administered safely and effectively alongside SSRIs and SNRIs, avoiding the medication tapers often advised for classical serotonergic psychedelics.^75,76

KAP, ketamine-assisted psychotherapy; NOSC, nonordinary state of consciousness; PAP, psychedelic-assisted psychotherapy; PSD, psychospiritual distress; SSRI, selective serotonin reuptake inhibitor; SNRI, selective serotonin and norepinephrine reuptake inhibitor.

Cofacilitation, clinical team composition, and training

Pal-KAP uses a cross-disciplinary, typically male/female facilitation dyad as a practical approach to meet PAP best practice standards for safety, ethics, and therapeutic depth.^77-80 This arrangement provides balanced clinical and emotional support, enhances safety for all patients, most particularly those with histories of sexual or physical trauma, models gender-sensitive and inclusive interaction, and mitigates potential boundary violations. Each session is cofacilitated by a lead facilitator (R.K.H. or M.T.S.) and a cofacilitator selected from a pool of specially trained clinicians, including nurses, advanced practice providers, mental health clinicians, and chaplains, chosen for relational sensitivity, attuned communication, and ethical integrity.

Facilitator dyads also foster mutual learning, professional growth, and enhanced care through structured pre-, intra-, and post-session dialogue, collaborative decision-making and processing with patients, and reflective debriefings that refine practice and deepen facilitation skills.

Training follows expert guidelines^77-80 and draws from palliative care competencies that mirror PAP demands, including compassionate presence, values-informed decisionmaking, cultural and spiritual sensitivity, trauma-informed care, ethical discernment, and recognition of illness-related vulnerabilities.^{64,65,69,81,82} It is provided through readings, didactics, off-site intensives, and an apprenticeship-like model in which new facilitators join the leads to learn on the job. The curriculum spans the history, pharmacology, phenomenology, and safety of ketamine and other psychedelics; psychotherapeutic approaches; relational ethics; and emergency responses. Ongoing supervision and reflective practice safeguard clinical integrity and facilitator well-being. Philanthropic support underwrites both off-site training and the facilitator dyad staffing model, fostering clinical expertise, team cohesion, and long-term sustainability.

Physical environment and start-up costs

Pal-KAP sessions are held in a dedicated room within the URMC outpatient palliative care clinic. Philanthropic support (~$25,000) funded the transformation of a standard examination room into a calm, quiet, and therapeutically supportive environment designed to promote patient comfort, safety, and openness. Figure 1 shows the resulting Pal-KAP room and key modifications that enhance the therapeutic setting.

FIG. 1.

The Pal-KAP room, adapted from a standard examination room to enhance comfort, safety, and therapeutic support. KAP, ketamine-assisted psychotherapy.

• Fully adjustable, medical-grade recliner accommodating patients of all sizes and physical abilities.

• Variable lighting, sound-dampening curtains, and carpet to support comfort and focus.

• Bluetooth-enabled speaker and over-ear headphones for music during the medicine session, with comfortable furnishings, and welcoming decor.

Operational funding and financial model

While new current procedural terminology (CPT) codes for PAP⁸³ hold future promise, insurers currently classify these treatments as “investigational”⁸⁴ and do not offer reimbursement. Despite this status, Pal-KAP maintains both fair patient access and program sustainability through a combination of standard billing practices and philanthropic support:

• Insurance billing: Pal-KAP sessions are billed using time-based Evaluation and Management (E/M) codes for medical providers and Psychotherapy codes for behavioral health providers. Documentation supports medical necessity, including diagnoses (usually the underlying serious illness plus the most appropriate mental health diagnosis, typically illness-related anxiety, adjustment disorder with anxiety or depressed mood, or major depressive disorder) and the type of care provided (exploratory supportive counseling for medical providers and psychotherapy for behavioral health providers). All sessions (preparation, medicine, and integration) are billed, except for the 45–60-minute NOSC period during the medicine session. Ketamine administration is documented, and the program absorbs the cost (typically <$20 per dose), as this indication is not reimbursed by insurance. The clinician with the higher reimbursement rate submits the shared session bill, including prolonged service codes as appropriate.

• Philanthropy: Ongoing philanthropic support covers most remaining shortfalls, including funding the cofacilitator, in order to provide care without charging patients beyond standard copays.

Clinical Workflow and Safety Infrastructure

Patient selection and screening

Patient selection is guided by clinical judgment and ethical responsibility, aiming to maximize benefit and minimize harm. Referrals undergo a structured two-step screening process:

1. Medical review: Comprehensive evaluation of medical records by the Pal-KAP medical director (R.K.H.), with consultation from the psychotherapy director (M.T.S.) as needed.

2. Patient assessment: Office visit to evaluate medical stability, psychological readiness, and alignment between the patient goals and values and the therapeutic framework.

Pal-KAP prioritizes the patient’s lived experience over standardized screening tools as the primary measure for assessing PSD, reflecting its individualized, variable, and subjective nature and the limitations of quantitative psychological and spiritual metrics in capturing its depth or meaning.^85-87 In Pal-KAP, PSD is defined by the patient and may include symptoms of depression, anxiety, demoralization, anticipatory grief, loss of meaning, or existential despair (see Box 2). Centering the patient’s own account ensures the program is accessible to those whose suffering may not conform to conventional metrics, prioritizes authentic engagement, and honors the complex, deeply personal nature of suffering in serious illness. In the palliative care context, this patient-centered approach also considers individual risk tolerance, recognizing that some patients facing life-limiting illness may reasonably accept higher medical risk to pursue meaningful therapeutic experiences.

Box 2. Pal-KAP Eligibility Criteria.

Inclusion criteria (all must apply):

1. Serious illness.*

2. Illness-related psychospiritual distress as defined by the patient, which may include symptoms of depression, anxiety, demoralization, anticipatory grief, loss of meaning, or existential despair.

3. Ability and openness to explore personal identity, meaning, and values.

Exclusion criteria:

1. History of psychosis, or active mania or hypomania.

2. More than mild cognitive impairment (e.g., due to dementia, developmental conditions, or illness- or treatment-related cognitive changes).

3. Pregnancy or breastfeeding.

Relative contraindications (require individualized risk–benefit assessment informed by patient priorities and goals)

1. Uncontrolled hypertension (>160/100 mm Hg)

2. Unstable heart disease

3. Recent cerebrovascular accident, new seizure, or brain metastasis with hemorrhagic risk

4. Severe pulmonary, renal, or liver disease

5. Severe active substance-use disorder

*By “serious illness,” we adapt Kelly⁸⁸: a medical condition with a high risk of both shortening life and imparting adverse impact on quality of life.

Informed consent and preparation

Pal-KAP emphasizes comprehensive informed consent as an ongoing, collaborative process, ensuring patients understand:

• Off-label ketamine use in KAP.

• Potential risks, including adverse physical and psychological reactions, retraumatization, changes in beliefs, and emotionally intense or misleading (“false”) insights or memories.^89,90

• The right to pause or discontinue treatment at any time without judgment.

• How physical support may be provided, including clear agreements around nonintimate touch.

• Confidentiality and data handling practices.

• Integration support following treatment.

This process prioritizes patient understanding, autonomy, and safety.

Session structure and facilitator roles

Pal-KAP sessions follow a three-step sequence typical of PAP and KAP models, informed by both indigenous healing traditions and contemporary adaptations.^{28,29,50,91-96} All sessions are cofacilitated by two trained clinicians to foster safety, relational balance, and ethical integrity. Medicine sessions are conducted on-site, while preparation and integration sessions may be conducted virtually when appropriate or preferred.

1. Preparation session (1 hour): Establish the therapeutic relationship; review patient background and goals; provide psychoeducation on KAP; explain the medicine session process; discuss music selection, use of eyeshades, recliner set-up, and preferences regarding physical support; rehearse strategies (e.g., hand-hold, hand-to-shoulder, verbal reassurance) for managing anxiety or distress during sessions; guide intention-setting to prime the medicine experience; and complete the informed consent.

2. Medicine session (2.5–3 hours): Reinforce preparation and intention-setting; administer intramuscular ketamine; attend to the patient’s experience, comfort, and safety; and document recalled experience (e.g., imagery, emotions, and insights) without analytic interpretation for later integration.

3. Integration session (1 hour): Process the medicine session experience; assess emotional and cognitive shifts; and collaboratively identify and strengthen personally meaningful practices (e.g., meditation, reflective writing, time in nature, mindful awareness) that support continued self-understanding, self-acceptance, and presence.

Pal-KAP’s psychotherapeutic framework

Psychotherapeutic approaches within KAP, and PAP more broadly, range from nondirective support to structured modalities and innovative blends.^97-104 Debates persist regarding which models are most effective,^102,105 whether formal psychotherapy is necessary,^106-109 and even whether psychotherapy is the appropriate term.¹⁰⁷ Similar to many in the PAP field, we hold that the essential elements of Pal-KAP’s psychotherapeutic process are relational attunement, ethical practice, and safety-conscious, compassionate engagement.^110-114 Healing in Pal-KAP is not contingent on fidelity to a specific psychotherapeutic school or method, but on the quality of therapeutic relationships, the patient’s trust amid vulnerability during the NOSC, and the facilitators’ capacity to hold and support that experience with competence and care.

We use the term psychotherapy deliberately—not to align with a particular theoretical orientation, but to reflect an intentional, therapeutic, and relational practice oriented toward the care of the psyche. The approach is psychologically informed, aimed at actively engaging patients to explore the meaning of their experience and integrate it into their life in a way that supports durable positive change.

Dosing strategy and emergency planning

We use intramuscular (IM) ketamine because it is simple to administer, pharmacokinetically reliable, and inexpensive (typically under $20 per 5-ml vial at standard pharmaceutical pricing). The prescribing clinician can order, draw up, and administer the IM injection directly, whereas intravenous ketamine usually requires an additional clinician for line placement and an infusion pump, increasing cost and potentially disrupting the therapeutic environment. IM administration achieves high and consistent bioavailability (~93%),¹¹⁵ with predictable onset and duration. By contrast, sublingual (19–49%),^116,117 oral (17–27%),¹¹⁶ and intranasal (25–50%)^118,119 routes show greater variability in absorption and are less readily accessible and more expensive, as they generally require compounding by specialty pharmacies.^120,121

Dosing is individualized based on patient age, frailty, body composition, prior exposure to psychoactive substances, previous ketamine response, treatment goals, and clinician judgment. Although serum concentration and subjective effects vary across individuals at a given dose,¹²² we begin within a conservative, evidence-based range and titrate based on these factors, published pharmacokinetics, and clinical experience.

Doses typically range from 0.8 to 1.2 mg/kg IM, as ~ 1.0 mg/kg IM produces plasma levels within the 50–200 ng/ml range reliably associated with a NOSC.^122,123 This aligns with reports from community KAP practices,³⁸ where average IM doses of 80–90 mg correspond to ~0.8 to 1.4 mg/kg IM in average-weight U.S. adults. If the desired effect is not achieved, a booster dose, typically 50% of the initial amount, may be administered after five to seven minutes, although in our experience this occurred in only 3 of 50 sessions. Per our institutionally approved Pal-KAP guideline, first-session doses are capped at 1.0 mg/kg IM, with subsequent session doses titrated up to 1.5 mg/kg IM as clinically indicated.

Pal-KAP is initiated with a single planned medicine session, without expectation of additional sessions. This allows patients to assess subjective engagement and tolerability. Decisions to pursue further medicine sessions or adjust dosing are made jointly by patients and clinicians, considering perceived impact (including quality and integration of the NOSC, and insights gained), tolerability, and evolving medical status. Our patient population includes individuals with advanced illness; some who would have elected to continue were too medically frail to return, and one-third (10 patients) died during the first 28 months of the program described here. Among the remaining 20, several are considering additional work. Accordingly, the session counts reported in Table 2 reflect care delivered to date rather than final totals.

Table 2.

Pal-KAP Medicine Sessions, Dosing Patterns, and Adverse Effects (June 2023–September 2025)

Number of medicine sessions per patient	N	%
1	15	50.0
2	12	40.0
3	2	6.7
4	0	0
5	1	3.3
Total patients: 30
Mean sessions per patient: 1.7
Median sessions per patient: 1.5
Ketamine dose per session (mg/kg, IM) a	n (sessions)	%
0.5–0.79	6	12.0
0.8–0.99	21	42.0
1.0–1.19	18	36.0
1.2+	5	10.0
Total sessions: 50
Mean dose: 0.93 mg/kg (SD 0.18)
Median dose: 0.96 mg/kg
Adverse effects b	n (patients)	%
Anxietyc	5	16.7
Headache	3	10.0
Nausea	3	10.0
Insomnia	2	6.7
Dizziness	2	6.7
Vomitingd	1	3.3
Serious adverse eventse	0	0

^amg/kg: milligrams of ketamine per kilogram bodyweight; IM: intramuscular; we used adjusted body weight for obese patients (BMI >30) with the formula: Ideal Body Weight (IBW) + 0.4 × (Actual BW-IBW), adapted from published approaches. (Barras M, Legg A. Drug dosing in obese adults. Aust Prescr. Oct 2017;40 (5):189-193. doi:10.18773/austprescr.2017.053; Kim TK. Obesity and anesthetic pharmacology: simulation of target-controlled infusion models of propofol and remifentanil. Korean J Anesthesiol. Dec 2021;74(6):478-487; doi:10.4097/kja.21345.)

^bAdverse events were collected via facilitator observation and patient self-report in response to open-ended prompts about their experience in the 24 hours following medicine sessions.

^cClinically significant anxiety was defined as behavioral signs requiring facilitator intervention (handhold, hand to shoulder, verbal reassurance); mild/transient anxiety was common but not tabulated. Lorazepam was available but not required.

^dOne patient experienced intermittent vomiting for several hours after session in the context of recent highly emetogenic chemotherapy.

^eSerious adverse events were defined according to the FDA. (U.S. Food and Drug Administration: What is a Serious Adverse Event? Accessed September 14, 2025, https://www.fda.gov/safety/reporting-serious-problems-fda/what-serious-adverse-event.)

Emergency protocols address both medical and psychological events. Antihypertensives, antiemetics, and anxiolytics are available as indicated, with clear pathways for rapid clinical evaluation and transfer to higher-level care when needed. In the first 50 sessions, several nausea-prone individuals received prophylactic antiemetics, and one patient required clonidine for hypertension above threshold, with prompt resolution. Clinically significant anxiety, defined as behavioral distress requiring facilitator intervention, occurred in five patients and was managed using strategies rehearsed during preparation (hand-holding, hand-to-shoulder, and verbal reassurance). Lorazepam is available but has not been required.

Safety-first design: Core safeguards

Although ketamine has a well-established safety profile when administered in supervised medical settings,^124,125 Pal-KAP is not risk-free, particularly in seriously ill patients, where risks may be magnified. These include transient adverse effects (anxiety, headache, nausea, and dizziness),¹²⁶ misuse,¹²⁷ psychological injury,^90,128,129 and therapeutic misconduct.^130,131 To mitigate these potential harms and uphold patient safety, Pal-KAP integrates rigorous safeguards: careful patient screening, structured facilitator training, dual facilitation, comprehensive informed consent, on-site medicine administration, and clear emergency protocols. In our first 50 sessions, no serious adverse events occurred. Key program safeguards are summarized in Box 3.

Box 3. Key Safeguards.

1. Structured patient screening and assessment: Ensures medical and psychological appropriateness, readiness, and alignment between patient goals and the therapeutic framework.

2. Thoughtful facilitator selection, comprehensive training, and ongoing supervision: Supports safe, ethical, and effective care, including emergency preparedness.

3. Comprehensive informed consent and ongoing assent: Establishes shared understanding of safety protocols, communication expectations, and nonintimate touch tailored to patient preferences.

4. Diverse facilitator dyads: Promote relational balance, maintain ethical boundaries, and enhance safety.

5. In-person ketamine administration: Medicine sessions are conducted only under direct clinical supervision for in-person monitoring and immediate response; preparation and integration sessions may be conducted virtually when appropriate or preferred.

6. Clear emergency protocols: Enable rapid, organized

Patient profiles, treatment patterns, and outcomes

In May 2023, we launched the Pal-KAP program, providing palliative care, oncology, and neurology clinicians with guidance on indications and contraindications (Box 2). By September 2025, 59 patients had been referred for Pal-KAP screening, primarily by these clinical partners, along with three self-referrals. Of these, 43 (73%) met the eligibility criteria, and 30 (51%) elected to proceed with treatment. Nearly half of referred patients (n = 29) did not proceed to treatment, reflecting a mix of screening outcomes: 6 did not meet inclusion criteria; 10 were excluded due to medical or psychological contraindications; and 13 met all criteria but declined, most often due to psychological unease or ambivalence about experiencing a NOSC.

The first Pal-KAP patient session occurred in June 2023, and by September 2025, these 30 patients completed a total of 50 medicine sessions. Two were inpatients. All sessions took place in the dedicated Pal-KAP room—although program guidelines allow inpatient medicine sessions in the patient’s hospital room and, for suitable patients and circumstances, sessions at home, provided all safety, supervision, environmental, and therapeutic standards are met.

Demographics and referral characteristics for these 30 patients are summarized in Table 1, with session counts, dosing patterns, and adverse effects detailed in Table 2. Box 4 presents three illustrative patient vignettes highlighting the diversity of patient responses and the clinical relevance of KAP in palliative care.

Table 1.

Pal-KAP Patient Demographics and Referral Characteristics (June 2023–September 2025)

Characteristic	N	%	Mean	Median	SD
Age (19–76 years)	30	—	53.9	56	15.73
<26	1	3.3
26–35	3	10.0
36–45	4	13.0
46–55	7	23.3
56–65	6	20.0
66–75	7	23.3
76+	2	6.7
Gender
Female	16	53.3
-FAMABa	1	3.3
Male	14	46.7
-MAFABb	1	3.3
Race
White	29	96.7
Black	1	3.3
Primary serious illnessc
Cancer	24	80.0
Neurological disease	4	13.3
Eating disorder	2	6.6
Organ transplant	1	3.3
Referral source
Palliative care	15	50.0
Oncology	7	23.3
Neurology	3	10.0
Self	3	10.0
Adolescent medicine	2	6.7
Prognosis at entry
<6 months	4	13.3
-Hospice-enrolledd	2	6.6
6–12 months	2	6.6
1–2 years	1	3.3
Not stated	23	76.6

^aFAMAB, female, assigned male at birth; a subset of female.

^bMAFAB, male, assigned female at birth; a subset of male.

^cOne patient is counted in two categories.

^dHospice-enrolled patients are a subset of <6 months prognosis.

KAP, ketamine-assisted psychotherapy.

Box 4. Illustrative Vignettes: anonymized excerpts from actual kap sessions highlighting patients’ subjective experiences and emergent themes. these examples are descriptive and hypothesis-generating and are not offered as generalizable evidence.

Case 1. Person with progressing cancer; persistent self-criticism and impaired emotion regulation

Patient report (session 2 of 2):

• “Two people were crying, and they were me!”

• “I felt pure empathy for myself.”

Case 2. Person with chronic pain after heart transplant; fear of bodily betrayal and dying

Patient report (session 1):

• “I was a bird…soaring in the sun.”

• “I was so afraid of the transition…and now I know it’s gonna go smooth.”

Case 3. Person recently informed of six-month life expectancy; overwhelming death anxiety

Patient report (session 5 of 5):

• “Just me floating in a field of flowers.”

• “There are times I’m ready…and I’d be good with it.”

Ten pillars for Pal-KAP program development

As institutions consider whether and how to incorporate KAP into palliative care programs, it is essential to balance enthusiasm with caution and innovation with integrity. Our experience suggests that successful implementation depends not only on clinical skills and safety infrastructure but also on the ability to make a clear, value-based case to stakeholders. The strategies in Box 5 can help clinicians articulate their case effectively.

Box 5. Ten Pillars for Palliative Care KAP Program Development.

1. Lead with the need: Psychospiritual distress in seriously ill patients is a care gap KAP can help address.

2. Blend enthusiasm with rigor: Counter “psychedelic hype”^132,133 with careful planning and messaging that reflect both passion and precision.

3. Acknowledge the evidence: Be transparent about the strengths and the limitations of KAP and PAP research.

4. Leverage qualitative data: Use case series and patient narratives to provide real-world insight.

5. Prioritize safety and risk mitigation: Ensure expert oversight, clear protocols, informed consent, and safeguards such as dual facilitation.

6. Align with palliative care’s mission: Position KAP as a natural extension of whole-person, value-centered care.

7. Promote equitable access: Design programs that are inclusive, culturally sensitive, and financially accessible to diverse patients.

8. Foster interdisciplinary collaboration: Engage diverse teams to strengthen both process and outcomes.

9. Strive for financial sustainability: Leverage mission-aligned philanthropy in addition to judicious billing and documentation to sustain delivery of this innovative therapeutic approach.

10. Apply the palliative care ROI framework: Judge true success by patient and family outcomes, including quality of life and psychospiritual well-being.

KAP, ketamine-assisted psychotherapy; PAP, psychedelic-assisted psychotherapy; ROI, return on investment.

Discussion

This work presents the first 28 months of the Pal-KAP program, designed to address psychospiritual distress (PSD) in seriously ill patients. We describe the program’s rationale, development, clinical design, financial model, safety structure, patient metrics, and three illustrative vignettes. To our knowledge, this represents the largest published cohort of KAP in an academic palliative care context. Our experience demonstrates that a KAP program can be embedded effectively and safely in a palliative care setting. The vignettes illustrate a small sample of the types of patient experiences observed and provide a signal of the program’s potential benefit for PSD.

This is consistent with observational studies indicating benefits of KAP for depression, anxiety, PTSD, and related challenging emotional states,^{38,61,134,135} as well as broader PAP research suggesting that supported NOSCs may help alleviate existential suffering and PSD.^{34,50,136-138} While these findings are encouraging, randomized controlled trials would provide more rigorous estimates of effect sizes and clarify benefits and harms under more controlled conditions.

Several limitations warrant consideration. Our patients were predominantly White (96%), compared with the more diverse racial composition of our region,¹³⁹ reflecting underrepresentation of Black and other minoritized populations in psychedelic research and clinical care.^140-142 Structural inequities, mistrust rooted in historical harms, and socioeconomic barriers likely contribute.^142-144 The cohort also was primarily patients with cancer, and while it included some diversity in age and gender identity, these limitations restrict generalizability to other populations and diagnoses.

Another limitation is that over the 28-month program period described, 10 of 30 patients (one-third) died, underscoring the extreme illness of this population. Several surviving patients have expressed interest in additional sessions; thus, Table 2 reflects cumulative exposure to date rather than final totals. These factors should be considered when interpreting session frequency and program engagement.

Implementation of Pal-KAP benefited from substantial philanthropic support, resource-intensive specialized training, institutional commitment, and controlled therapeutic environments, conditions that may not exist else-where. These resource demands underscore the challenges of exploring, launching, and sustaining a program such as Pal-KAP.

Future work, including our planned qualitative cohort study, will explore patient experiences more systematically, providing richer insights into the subjective and psychospiritual dimensions of KAP in palliative care. Building on these preliminary findings, future work could include coordinated, multisite qualitative, and mixed-methods research to capture diverse patient experiences and inform broader implementation of KAP.

Conclusion

The first 28 months of Pal-KAP demonstrate that KAP can be delivered safely and ethically in an academic palliative care setting, while highlighting important caveats regarding evidence, equity, and scalability. By emphasizing clinical rigor, interdisciplinary collaboration, and structured safety practices, this program offers a preliminary blueprint for other teams considering similar initiatives. At the same time, the evidence remains preliminary, the cohort demographically narrow, and implementation dependent on substantial institutional and philanthropic support, all of which limit generalizability. Future research, including multisite qualitative and mixed-methods studies across diverse populations and diagnostic groups, will be essential to clarify feasibility, equity, generalizability, and effectiveness. Pal-KAP demonstrates that thoughtfully designed KAP can be delivered safely and ethically, offering a practical model for addressing PSD in seriously ill patients.

Key Message.

Pal-KAP illustrates that ketamine-assisted psychotherapy is feasible in palliative care and offers a practical blueprint for safely addressing psychospiritual distress in people with serious illness.