Mapping an Agenda for Psychedelic-Assisted Therapy Research in Patients with Serious Illness

Beaussant and colleagues frame the problem by noting that people with serious illness frequently experience psychological, existential, and spiritual distress that negatively affects quality of life and other health outcomes. The introduction summarises prior findings that more than 30% of patients with cancer meet criteria for mood disorders such as anxiety or depression, and 13%-18% present clinically relevant demoralization. It also notes that conventional pharmacological, psychological, and spiritual care interventions often produce only small to moderate effect sizes, while preliminary studies of psychedelic-assisted therapies suggest potentially large and persistent improvements in depression, anxiety, existential distress, spiritual well-being, and quality of life among seriously ill patients. At the same time, experts have raised concerns about adverse effects (for example, delirium or worsening psychological distress), ethical issues around consent and therapeutic boundaries, and the need for rigorous research as legal and regulatory landscapes evolve. The paper reports an exploratory effort to define research priorities for psychedelic-assisted therapies in serious illness. To that end, the authors convened an interdisciplinary seminar bringing together clinicians and researchers from palliative care, psychosocial oncology, spiritual care, oncology, and psychedelic-assisted therapy. The stated aim was to elicit participant perspectives and to map an agenda for future research, identifying key domains where empirical work and institutional change are required. The authors emphasise the study’s pragmatic purpose: to synthesise expert input to guide rigorous, ethically grounded research in this emerging field.

The investigators organised a two-day seminar at the Radcliffe Institute for Advanced Study (Harvard University) in January 2020, designed to generate interdisciplinary perspectives on priorities for psychedelic-assisted therapy research in serious illness. The seminar agenda drew on preconference phone interviews with invitees to shape discussion topics and expectations. The extracted text indicates that 19 participants were invited; elsewhere in the paper the Discussion reports an interdisciplinary group of 23 clinicians, researchers, and one patient, so attendee numbers are not reported consistently in the extracted material. Attendees represented expertise in palliative care, psychology, psychiatry, oncology, spiritual care, and psychedelic research; one participant was a patient with advanced cancer formerly enrolled in a psilocybin trial. Data collection combined several qualitative sources: audio recordings of large- and half-group sessions, flip charts and sticky notes from small-group work, and contemporaneous notes taken by two authors. The study was designated Not Human Subject Research by the Dana-Farber Cancer Institute's Office for Human Research Studies. For analysis, the team used thematic qualitative methods implemented in Dedoose (version 8.3.19): one author (Y.B.) coded the recorded data, then organised and reduced codes using an open grid to allow themes to emerge. Conceptualisation of final themes resulted from discussion among coauthors and some participants. The seminar also employed structured facilitation techniques (for example, importance/likelihood and creative matrices) to generate and prioritise ideas. All participants were offered the opportunity to review the manuscript.

Thematic analysis identified seven priority topic areas for advancing psychedelic-assisted therapy research in serious illness. Four priorities related to research design and science: clarifying indications and outcomes, developing and standardising therapeutic protocols, investigating the role of the therapeutic setting, and elucidating mechanisms of action. Three priorities addressed institutional and societal drivers: education and certification for therapists, regulatory and funding frameworks, and diversity and inclusion in research and clinical programmes. On indications and outcomes, participants urged standardisation of outcome measures across studies and emphasised the particular importance of existential and spiritual dimensions of suffering. They proposed a wide set of candidate outcomes spanning patient and family domains (e.g., depression, anxiety, demoralization, spiritual well-being, quality of life, caregiver mental health and bereavement). The group suggested that psychedelic-assisted therapies could help ‘‘map the landscape of existential distress’’ and called for work to disentangle and operationalise constructs such as spiritual versus existential suffering. Potential adverse relational effects were also raised; for example, one participant referenced literature suggesting relationship disruption after profound experiences and recommended monitoring negative relational outcomes. Regarding therapeutic protocols, participants recommended manualising psychotherapeutic support across preparation, dosing sessions, and integration. They proposed comparing different psychedelic agents (including shorter-acting compounds such as DMT or ketamine for frail patients) with one another and with existing standard-of-care psychosocial interventions. Integration of psychedelic-assisted therapies with evidence-based approaches common in serious illness care (for example, meaning-centred therapy or acceptance and commitment therapy) and with spiritual care (e.g., chaplaincy) was highlighted. Participants also discussed therapeutic modalities (individual, conjoint, group) and the possible inclusion of caregivers in trials. On setting, seminar attendees discussed criteria for treatment spaces (comfortable, quiet, aesthetic, private rooms with appropriate audio systems) and the importance of embedding research within interdisciplinary care models that ensure patients’ broader psychosocial and palliative needs are addressed. Concerns about unsafe or inappropriate settings, inadequate screening or preparation, and the risk that costs of specialised settings might exacerbate inequities were emphasised; some participants suggested institutions or insurers should absorb setting-related costs. For mechanisms of action, the group called for translational, mixed-methods research combining phenomenology, psychology, neuroimaging, and neurobiology to answer questions such as whether effects are driven by drug, psychotherapy, or their combination, what neural correlates (for example, ego dissolution) relate to therapeutic gains, and how traumatic resolution unfolds in this population. Institutional and societal themes included the need for education and standardised certification programmes for therapists, with curricula incorporating mentorship, supervision, diversity training, and debate about whether therapists should have personal experience with psychedelics or with other methods for expanded states of consciousness. Participants discussed regulatory and funding barriers and encouraged early engagement with agencies (for example, the FDA) and funding tied to inclusive recruitment. They also recommended strategies to make research and care inclusive—scholarships for therapists of colour, nontraditional recruitment sites, insurance coverage, and learning from indigenous knowledge and community models. Harm-reduction bridges between community and medical models were mentioned as possible complementary approaches. Finally, participants interrogated the suitability of a solely biomedical model for studying psychedelic-assisted therapies in serious illness, arguing that scientific frameworks may struggle to capture spiritual phenomena and that a broader multidisciplinary paradigm (including humanities and religious or indigenous perspectives) may be necessary to ask the right questions.

In their interpretation, the authors present the seminar findings as a roadmap identifying concrete research opportunities at the intersection of psychedelic-assisted therapies and serious illness care. They state that participants converged on the need to clarify patient and caregiver outcomes, refine therapeutic protocols and settings, and pursue mechanistic research—while also addressing systemic requirements such as therapist training, funding and regulatory reforms, and inclusive research practices. The paper situates these priorities within a broader rationale: limited efficacy of current interventions for psychosocial and existential distress and the potential public-health value of effective new approaches. The authors relate the seminar outcomes to earlier qualitative work and to the growing interest in mainstream psychedelic research for seriously ill populations. They also note that the SARS-CoV-2 pandemic has intensified psychosocial and existential distress for patients, families, and professionals and that racial trauma and inequities further compound need, underscoring the urgency of thoughtful research and equitable access. The discussion highlights epistemological tensions: some participants argued that the biomedical model may inadequately capture spiritual dimensions, while others advocated maintaining mechanistic approaches to ensure reproducible science. The authors suggest that reconciling these perspectives may require research grounded in biomedicine but informed by humanities and indigenous and religious expertise. Limitations acknowledged by the authors include incomplete representation of relevant stakeholders (for example, nurses, spiritual care providers, representatives of indigenous groups, industry and regulatory actors), underrepresentation of women and people of colour among participants, and methodological constraints of an exploratory seminar format. The authors note that alternative consensus methods (for example, a Delphi process) or narrower methodological focus might yield additional insights and recommend these approaches for future work.

The paper concludes that the seminar participants identified multiple priority domains to advance psychedelic-assisted therapy research for people affected by serious illness, spanning clinical, mechanistic, and institutional issues. The authors argue that pursuing these priorities could improve evidence-based understanding of patient and family needs at end of life, support integration of psychedelic-assisted therapies into serious illness care, and enable interdisciplinary approaches to relieve psychosocial and existential suffering. They add that legal rescheduling of psychedelics and allocation of federal funds will likely be important enablers for a meaningful research programme.