Psilocybin-Assisted Therapy Improves Psycho-Social-Spiritual Well-Being in Cancer Patients


Sarah Shnayder, Rezvan Ameli, Ninet Sinaii, Ann Berger, Manish Agrawal 

Originally published in The Journal of Affective Disorders as Psilocybin-assisted therapy improves psycho-social-spiritual well-being in cancer patients.

Published Date: February 15, 2023



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.


In this Phase II, single-center, 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 adjacent 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.


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).


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.


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 underlying elements for psycho-social-spiritual healing in cancer patients, and validates the use of the NIH-HEALS within psychedelic research.


A cancer diagnosis can have a devastating effect on physical, psychological, and spiritual well-being (Niedzwiedz et al., 2019; Zare et al., 2019). While extensive focus has been placed on mitigating the physiological impact, recent efforts have aimed to uncover the psycho-spiritual needs of cancer patients (Hatamipour et al., 2015; Astrow et al., 2018). Many cancer patients experience clinical depression and anxiety (Zabora et al., 2001; Mitchell et al., 2011), a debilitating fear of dying, disconnectedness, lack of control, and loss of hope (Coward and Kahn, 2004; Moreno and Stanton, 2013). Yet, traditional pharmacotherapeutics have mixed and limited efficacy in treating cancer-related distress (Li et al., 2012).

Psychedelic therapies such as psilocybin (Griffiths et al., 2016) are among novel therapeutic approaches that have found a renewed relevance in recent years. Throughout history, Indigenous tribes have utilized plant-based hallucinogenic substances for their healing properties. These ceremonies promoted mystical experiences, open-mindedness, and connection with nature and the divine (Carod-Artal, 2015; Nichols, 2020). During the 1960s–1970s, psychedelic research in the United States documented profound effects on psychological health, quality of life, and pain in cancer patients (Kast and Collins, 1964; Kast, 1966; Pahnke, 1969). However, safety concerns were raised in response to widespread non-medical use, and clinical research was halted with the Controlled Substance Act. Since then, conditions for safe administration, proper set and setting, and a code of ethics for psychedelic use have been established (Johnson et al., 2008; Mithoefer, 2017). In more recent clinical trials, psilocybin was found to promote significant and substantial improvements in cancer-related depression, anxiety, existential distress, and orientation towards death (Grob et al., 2011; Griffiths et al., 2016; Ross et al., 2016). While the effects are clear, the mechanistic underpinnings of psychedelic-mediated psycho-spiritual change in cancer patients are less understood.

A recently validated measure, the NIH-HEALS, has been developed based on interviews with patients who experienced positive psychological, social, and spiritual change after being diagnosed with severe and/or life-threatening diseases. Two hundred patients, 80 % of whom had diagnoses of cancer, were recruited from the NIH Clinical Center and participated in the validation of the NIH-HEALS. Results showed the measure to have high internal consistency, split-half reliability, and convergent and divergent validity (Ameli et al., 2018). Factor analysis of the NIH-HEALS yielded three primary elements instrumental in psycho-social-spiritual healing: (1) Connection: a sense of religious, spiritual and interpersonal connectedness (2) Reflection & Introspection: a sense of meaning, purpose, and gratitude, experience of joy in nature, use of activities that connect mind and body, present moment orientation, and an awareness about the fragility of life; (3) Trust & Acceptance: the ability to let go of resistance, to feel resolved and at peace with one’s circumstances, and to trust that caregivers, friends and family will respond to needs as they arise. These factors are consistent with cancer literature, as higher well-being in cancer patients has been linked to one’s connectedness with others (Lin and Bauer-Wu, 2003), sense of life-meaning (Lin and Bauer-Wu, 2003; Sleight et al., 2021), and acceptance of the diagnosis (Secinti et al., 2019).

The factors of connection, reflection &introspection, and trust &acceptance are also influenced by psychedelic therapy. Subjective reports indicate that psychedelic therapy can improve one’s sense of connection, as participants have described experiences of reduced self-other boundaries (Smigielski et al., 2020), increased nature relatedness (Kettner et al., 2019), and a profound sense of oneness with all (Watts et al., 2017). Psychedelic therapy is also thought to promote introspection by leading one on an exploration of the unconscious, to discover all disavowed aspects of the self and begin a process of attachment repair (Vaid and Walker, 2022). Lastly, psychedelics may encourage acceptance, as attempts to exert control over a challenging psychedelic experience typically fail while adopting an allowing attitude and letting go provides the intended relief (Wolff et al., 2020). This encounter teaches one to move towards suffering rather than away, transforming habitual avoidance into a growth-inclined attitude (Watts et al., 2017).

We hypothesize that the elements of Connection, Reflection & Introspection, and Trust & Acceptance underlie the psycho-social-spiritual improvements evidenced in psilocybin therapy. Thus, the present study aims to evaluate the changes in NIH-HEALS scores in a cancer population with major depressive disorder following psilocybin-assisted therapy.

Study design

This was a Phase II, single-center, fixed dose, open label trial of psilocybin-assisted group therapy in cancer patients with Major Depressive Disorder (MDD). Psychotherapeutic care was provided before, during, and after psilocybin administration to cohorts of 3–4 participants. Supportive therapy included individual and group preparation sessions, simultaneous administration of psilocybin to the cohort, and individual and group integration sessions.


Demographic information describing the sample is presented in Table 2. The mean age of participants was 56 years (SD 12). Participants did not identify outside of the gender binary, with 30 % identifying as male and 70 % as female. The sample was predominantly Caucasian (80 %), married (67 %), and employed (83 %). Most participants (70 %) had undergone >1 line of cancer therapy. At baseline, participants had a mean HAMD score of 25.4 and mean QIDS score of 12.3, both of which indicate moderate


In this study, cancer patients with depression experienced marked improvements in psycho-social-spiritual wellbeing following psilocybin-assisted therapy, as assessed by the NIH-HEALS. These improvements occurred within the domains of Connection, Reflection & Introspection, and Trust & Acceptance, and were sustained for up to 8 weeks post-dosing. Thus, the results of this study demonstrate that the NIH-HEALS was a useful measure in the context of psychedelic research, and point to a potential

Credit authorship contribution statement

Manish Agrawal—Contributed to acquisition, analysis, interpretation of data for the article, design of the article, revised critically.

Ann Berger—Revised article critically for important intellectual content.

Rezvan Ameli—Contributed to design of the article, interpretation of the data, revised article for important intellectual content.

Sarah Shnayder- Contributed to design of article, interpretation of data and drafted the article.

Ninet Sinaii—Contributed to statistical analysis of the article.

Conflict of interest

The authors confirm that the article content has no conflict of interest.


Declared none.



A.B. Astrow et al.Spiritual needs and perception of quality of care and satisfaction with Care in Hematology/Medical oncology patients: a multicultural assessment
J. Pain Symptom Manag.


D. BenorThe definition of healing depends on how one defines health
Explore (New York, N.Y.)


F.J. Carod-ArtalHallucinogenic drugs in pre-columbian mesoamerican cultures
Neurología (English Edition)


A.J. Mitchell et al.Prevalence of depression, anxiety, and adjustment disorder in oncological, haematological, and palliative-care settings: a meta-analysis of 94 interview-based studies
Lancet Oncol.


E. Secinti et al.The relationship between acceptance of cancer and distress: a meta-analytic review
Clin. Psychol. Rev.


R. Ameli et al.The National Institutes of Health measure of healing experience of all life stressors (NIH-HEALS): factor analysis and validation
PloS one


M.J. Brady et al.A case for including spirituality in quality of life measurement in oncology


D.D. Coward et al.Resolution of spiritual disequilibrium by women newly diagnosed with breast cancer
Oncol. Nurs. Forum


R.R. Griffiths et al. Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: a randomized double-blind trial
J. Psychopharmacol.


L. Grinspoon et al.Psychedelics as catalysts in insight-oriented psychotherapy
Soc. Res.


C.S. Grob et al. Pilot study of psilocybin treatment for anxiety in patients with advanced-stage cancer
Arch. Gen. Psychiatry


S. GrofImplications of modern consciousness research for psychology: holotropic experiences and their healing and heuristic potential
Humanist. Psychol.


M. HamiltonA rating scale for depression
J. Neurol. Neurosurg. Psychiatry


K. Hatamipour et al.Spiritual needs of cancer patients: a qualitative study
Indian J. Palliat. Care


J.C. Holland et al.Psycho-oncology

M.W. Johnson et al.Human hallucinogen research: guidelines for safety
J. Psychopharmacol.


E. KastLSD and the dying patient
Chic. Med. Sch. Q.


E.C. Kast et al.Study of lysergic acid diethylamide as an analgesic agent
Anesth. Analg.


H. Kettner et al.From egoism to ecoism: psychedelics increase nature relatedness in a state-mediated and context-dependent manner
Int. J. Environ. Res. Public Health


X. Li et al.Review of pharmacological treatment in mood disorders and future directions for drug development


H.-R. Lin et al.Psycho-spiritual well-being in patients with advanced cancer: an integrative review of the literature
J. Adv. Nurs.