This pre-print open-label trial (n=30) assessed psycho-spiritual change in cancer patients with major depressive disorder after a single dose of psilocybin (25mg). Participants underwent individual and group preparation and integration sessions, while the NIH-HEALS was used to assess psycho-spiritual change. Across all three factors (Connection, Reflection and Introspection) of the NIH-HEALS, psilocybin led to positive changes at all time points.
Papers cited by this study that are also in Blossom
Griffiths, R. R., Johnson, M. W. · Journal of Psychopharmacology (2016)
Background
While psychedelics have been shown to improve psycho-spiritual well-being, the underlying elements of this change are not well-characterized. The NIH-HEALS posits that psycho-social-spiritual change occurs through the factors of Connection, Reflection $ Introspection, and Trust $ Acceptance. This study aimed to evaluate the changes in NIH-HEALS scores in a cancer population with major depressive disorder undergoing psilocybin-assisted therapy.
Methods
In this Phase II, single-centre, open-label trial, 30 cancer patients with major depressive disorder received a fixed dose of 25 mg of psilocybin. Participants underwent group preparation sessions, simultaneous psilocybin treatment administered in separate rooms, and group integration sessions, along with individual care. The NIH-HEALS, a self-administered, 35-item measure of psycho-social spiritual healing, was completed at baseline and post-treatment at day 1, week 1, week 3, and week 8 following psilocybin therapy.
Results
NIH-HEALS scores, representing psycho-social-spiritual wellbeing, improved in response to psilocybin treatment (p < 0.001). All three factors of the NIH-HEALS (Connection, Reflection $ Introspection, and Trust $ Acceptance) demonstrated positive change by 12.7 %, 7.7 %, and 22.4 %, respectively. These effects were apparent at all study time points and were sustained up to the last study interval at 8 weeks (p < 0.001).
Limitations
The study lacks a control group, relies on a self-report measure, and uses a relatively small sample size with limited diversity that restricts generalizability.
Conclusions
Findings suggest that psilocybin-assisted therapy facilitates psycho-social-spiritual growth as measured by the NIH-HEALS and its three factors. This supports the factors of Connection, Reflection $ Introspection, and Trust $ Acceptance as important elements for psycho-social-spiritual healing in cancer patients and validates the use of the NIH-HEALS within psychedelic research.
Shnayder and colleagues frame the study around the substantial psycho-social and spiritual burden that can accompany a cancer diagnosis, including depression, anxiety, fear of dying, disconnection and loss of meaning. They note that traditional pharmacotherapies have limited and mixed efficacy for cancer-related distress, and that psychedelic-assisted therapies such as psilocybin have re-emerged as promising interventions. Earlier clinical research and recent trials suggest psilocybin can produce large improvements in cancer-related depression, anxiety and existential distress, but the mechanisms underlying psycho-spiritual change remain incompletely characterised. The investigators focus on the NIH-HEALS, a validated 35-item self-report instrument developed from interviews with patients facing severe or life‑threatening illness; factor analysis of the measure yielded three interrelated domains thought to underpin healing: Connection, Reflection & Introspection, and Trust & Acceptance. The present study was designed to evaluate change in NIH-HEALS scores in a sample of cancer patients with Major Depressive Disorder following a fixed 25 mg dose of psilocybin administered with preparatory and integration psychotherapy. The stated aim was to test whether psilocybin-assisted therapy produces measurable improvements on the NIH-HEALS and thereby provide evidence about the psychological elements that mediate psycho-social-spiritual change.
This was a Phase II, single-centre, fixed-dose, open‑label trial of psilocybin-assisted group therapy conducted at a cancer centre in Rockville, Maryland. Thirty participants were recruited over eight months by convenience sampling from the study site and referrals; written informed consent was obtained. Inclusion criteria were age ≥ 18 years, a DSM‑5 diagnosis of Major Depressive Disorder (single or recurrent) without psychotic features, a baseline Hamilton Depression Rating Scale (HAMD) score ≥ 18, and a malignant neoplasm (ICD‑10 C00–C97). Exclusion criteria followed standard psilocybin safety guidelines and included current or past psychotic disorder, bipolar disorder, borderline personality disorder, or significant suicide risk. Psychiatric medications were tapered per usual psychedelic research practice; participants continued oral cancer medications and no cancer procedures were performed during the study. Participants were treated in cohorts of 3–4 and completed eight visits across an 8‑week period. The therapeutic programme comprised individual and group preparatory sessions, simultaneous psilocybin administration in separate rooms with assigned therapists present, and individual and group integration sessions. The dosing visit (Visit 3) delivered 25 mg psilocybin; the in-session approach was non‑directive, used eyeshades and a music programme to promote an inner-directed experience, and therapists emphasised active listening and presence rather than interpretation or advice. Outcome measurement focused on the NIH‑HEALS, administered at baseline (Visit 2) and at week 1 (V5), week 3 (V6), and week 8 (V7) post‑treatment. The NIH‑HEALS is a 35‑item, 5‑point Likert measure (total score range 35–175) with three correlated factors: Connection, Reflection & Introspection, and Trust & Acceptance. For analysis, the investigators used mixed models for repeated measures to assess NIH‑HEALS scores over time, adjusting for baseline NIH‑HEALS, age (continuous) and gender (categorical). Post-hoc comparisons used Dunnett's method with baseline as the referent and analyses were conducted in SAS v9.4. The extracted text does not state whether an intention‑to‑treat principle was applied or give detailed sample‑level demographic breakdowns in the Methods section.
Data are described using frequency (percentage) for categorical data and mean (SD) for continuous data and were assessed for distributional (normality) assumptions. Mixed models for repeated measures were used to analyze NIH-HEALS scores (outcome, dependent variable, continuous data) at each visit over time (week 1, week 3, week 8). These models adjusted for baseline NIH-HEALS score, as is required in repeated measures analysis. In addition, models were adjusted for potential confounding effects of age (continuous) and gender (categorical). Post-hoc comparisons adjusted for multiple comparisons by Dunnet's method with baseline as the referent comparison. Data were analyzed using SAS v9.4 (SAS Institute, Inc, Cary, NC).
In placed on enhancing the development of these factors during therapeutic sessions. For example, therapists leading preparation and integration sessions can emphasize themes of connection, teach mindfulness skills, promote acceptance of life's circumstances, and encourage awareness of the fragility of life awareness. This existential awareness, so called -double awareness‖ on life and death, vitalizes people to live more fully, while also preparing them for the inevitable transition. The renewed interest in psilocybin therapy represents a paradigm shift towards a more holistic approach to treatment. There is an underlying assumption that the psyche holds the tools for its own healing, with psychedelics acting as its catalyst. This therapy also addresses the complexity of the whole person, including the mind, body, and spirit. While the mind and body have traditionally been regarded as important dimensions, it is noteworthy that the medical field is evolving to incorporate spiritual wellbeing into its definition of health. Spirituality was found to be associated with quality of life to the same degree as physical well-being. Thus, the inclusion of this domain of life in treatment aligns with the current knowledge base on the factors contributing to wellbeing, healing, and quality of life. Addressing psycho-spirituality might be particularly salient in the cancer patient population, whose diagnoses have radically restructured their lives. In order to experience meaning in life, humans need to comprehend the world around them (coherence), find direction for their actions (purpose), and find worth in their lives (significance). Diagnosis of severe and/or life-threatening disease can shatter one's sense of coherence, basic safety, purpose, and significance. However, those who are able to reformulate the world around them and their place within it can emerge on a growth trajectory, with a greater sense of wholeness than before their diagnosis. Psilocybin is one tool that has the potential to facilitate this transformation in patients by encouraging acceptance of their disease, increasing trust in caregivers, expanding their perspective of self, and deepening a sense of connection to self, others, nature, or a higher power. J o u r n a l P r e -p r o o f The present study was limited by the lack of a control group, a potential for social desirability bias in responding to NIH-HEALS items, and a smaller sample size. In addition, the participants were predominantly Caucasian, female, and employed. These limitations should be considered in terms of the generalizability of the study results. Future studies may aim to reduce these limitations by including a control arm and repeating the treatment in a larger, more diverse sample. In summary, these findings bring a deeper understanding to the psycho-social-spiritual changes that emerge from psilocybin-assisted therapy, and will hopefully advance the psychedelic field.
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Grob, C. S., Danforth, A. L., Chopra, G. S. et al. · JAMA Psychiatry (2011)
Hartogsohn, I. · Frontiers in Human Neuroscience (2018)
Heifets, B. D., Malenka, R. C. · Cell (2016)
Johnson, M. W., Richards, W. A., Griffiths, R. R. · Journal of Psychopharmacology (2008)
Johnson, M. W. · ACS Pharmacology and Translational Science (2020)
Kettner, H., Gandy, S., Haijen, E. C. H. M. et al. · International Journal of Environmental Research and Public Health (2019)
Nichols, D. E. · Journal of Antibiotics (2020)
Ross, S., Bossis, A. P., Guss, J. et al. · Journal of Psychopharmacology (2016)
Preller, K. H., Herdener, M., Pokorny, T. et al. · Current Biology (2017)
Smigielski, L., Kometer, M., Scheidegger, M. et al. · Human Brain Mapping (2020)
Watts, R., Day, C. M., Krzanowski, J. et al. · Journal of Humanistic Psychology (2017)
Wolff, M., Evens, R., Mertens, L. J. et al. · Frontiers in Psychiatry (2020)
Papers in Blossom that reference this study
Back, A. L., McGregor, B. A., Thorn, L. L. et al. · Psychedelic Medicine (2026)
Beaussant, Y., Tarbi, E., Nigam, K. B. et al. · Cancer (2023)
Thirty participants completed the intervention and follow‑up visits; detailed demographic tables are not clearly reported in the extracted methods text, although the Discussion later indicates the sample was predominantly Caucasian, female and employed. Adverse events during the psilocybin sessions were generally mild and transient, resolving by the end of the treatment session. Reported treatment‑related adverse events and their frequencies included headache (80%), nausea (40%), tearfulness (27%), anxiety (23%), euphoria (23%), fatigue (23%), and mild impairment of psychomotor functioning (10%). The investigators reported no notable laboratory abnormalities, ECG changes, or emergence of suicidality. On the primary psycho‑social‑spiritual outcome, total NIH‑HEALS scores increased following psilocybin‑assisted therapy. The extracted results report an average increase of 16.4 points in the NIH‑HEALS total score by week 8, and this change was statistically significant (p < 0.001). Within the subscales, the extracted text explicitly reports an increase in the Trust & Acceptance factor of 22.4% by week 8 (p < 0.001). The extracted Results section does not clearly report numerical change or significance for the Connection and Reflection & Introspection factors in the body text, though the study hypothesis and other parts of the document indicate these domains were of interest. Post‑hoc comparisons were adjusted for multiple testing using Dunnett's method with baseline as the referent comparison.
Shnayder and colleagues interpret the findings as evidence that psilocybin‑assisted therapy can facilitate psycho‑social‑spiritual growth in cancer patients, particularly by enhancing acceptance and trust, and by encouraging existential reflection and connection. They propose that therapeutic processes in preparation and integration sessions can be oriented to cultivate the NIH‑HEALS factors — for example, by emphasising connection, teaching mindfulness skills, promoting acceptance, and encouraging awareness of life's fragility. The authors situate these effects within a broader paradigm shift toward holistic treatment that recognises spiritual wellbeing alongside physical and psychological health. The investigators acknowledge several important limitations. The trial was open label and lacked a control arm, which limits causal inference. Use of a self‑report measure introduces potential social desirability or reporting bias. Sample size was relatively small and participant demographics were limited, reducing generalisability; specifically, the sample was predominantly Caucasian, female and employed. The authors recommend that future research include controlled designs and larger, more diverse samples to replicate and extend these findings. They conclude that the results deepen understanding of the psycho‑social‑spiritual changes associated with psilocybin therapy and support the relevance of the NIH‑HEALS factors for assessing such change.