Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: A randomized double-blind trial
Griffiths, R. R., Johnson, M. W., Carducci, M. A., Umbricht, A., Richards, W. A., Richards, B. D., Cosimano, M. P., & Klinedinst, M. A. (2016). Journal of psychopharmacology (Oxford, England).
Methodology: Randomized double-blind cross-over trial. Each participant received a very low placebo-like dose (1 or 3 mg/70 kg) in one session and a high therapeutic dose (22 or 30 mg/70 kg) in another session ~5 weeks later (order randomized). Sessions were conducted in a supportive setting with monitored psychotherapy, and outcomes were assessed up to 6 months.
Sample: Evaluating psilocybin for depression/anxiety in 51 patients with life-threatening cancer.
Dosage: 1 or 3 mg/70 kg and 22 or 30 mg/70 kg
Key Findings:
– The high-dose psilocybin session produced large, immediate reductions in depression and anxiety, alongside increases in quality of life, meaning, and optimism, and decreased death anxiety.
– Impressively, at 6-month follow-up ~80% of participants still showed clinically significant relief from depression and anxiety symptoms. – – Participants attributed positive changes in life attitude, mood, relationships, and spirituality to the psilocybin experience, with >80% reporting increased well-being or life satisfaction.
– Mystical-type psilocybin experience on session day mediated the effect of psilocybin dose on therapeutic outcomes.
Implications: This landmark RCT demonstrated substantial and sustained anxiolytic and antidepressant effects of a single psilocybin session in distress related to terminal illness.
Citation: Griffiths, R. R., Johnson, M. W., Carducci, M. A., Umbricht, A., Richards, W. A., Richards, B. D., Cosimano, M. P., & Klinedinst, M. A. (2016). Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: A randomized double-blind trial. Journal of psychopharmacology (Oxford, England), 30(12), 1181–1197. https://doi.org/10.1177/0269881116675513
Rapid and sustained symptom reduction following psilocybin treatment for anxiety and depression in patients with life-threatening cancer: a randomized controlled trial
Ross, S., Bossis, A., Guss, J., Agin-Liebes, G., Malone, T., Cohen, B., Mennenga, S. E., Belser, A., Kalliontzi, K., Babb, J., Su, Z., Corby, P., & Schmidt, B. L. (2016). Journal of psychopharmacology (Oxford, England).
Methodology: Randomized double-blind placebo-controlled cross-over trial. Patients received a single moderate dose of psilocybin in one session and a placebo (niacin) in another session (with random order), each combined with preparatory and follow-up psychotherapy. Symptoms of anxiety and depression were measured at 7 weeks (prior to crossover) and again long-term.
Sample: Focused on cancer-related existential distress in 29 patients.
Dosage: 0.3 mg/kg of psilocybin
Key Findings:
– The psilocybin treatment led to “rapid and sustained” reductions in anxiety and depression, along with decreased demoralization and hopelessness and improved spiritual well-being and quality of life compared to placebo.
– By the 6.5-month follow-up (after all participants had received psilocybin), approximately 60–80% of participants were still experiencing clinically significant reductions in depression or anxiety.
Implications:
– Participants also reported lasting improvements in existential distress and attitudes toward death, indicating that a single psilocybin session (with therapy) can produce robust, enduring relief from end-of-life anxiety and depression.
– Notably, the intensity of the mystical-type experience induced by psilocybin was found to mediate its therapeutic outcomes, suggesting a link between profound subjective experiences and clinical efficacy.
Citation: Ross, S., Bossis, A., Guss, J., Agin-Liebes, G., Malone, T., Cohen, B., Mennenga, S. E., Belser, A., Kalliontzi, K., Babb, J., Su, Z., Corby, P., & Schmidt, B. L. (2016). Rapid and sustained symptom reduction following psilocybin treatment for anxiety and depression in patients with life-threatening cancer: a randomized controlled trial. Journal of psychopharmacology (Oxford, England), 30(12), 1165–1180. https://doi.org/10.1177/0269881116675512
Long-term follow-up of psilocybin-assisted psychotherapy for psychiatric and existential distress in patients with life-threatening cancer
Agin-Liebes, G. I., Malone, T., Yalch, M. M., Mennenga, S. E., Ponté, K. L., Guss, J., Bossis, A. P., Grigsby, J., Fischer, S., & Ross, S. (2020). Journal of psychopharmacology (Oxford, England).
Methodology: Long-term follow-up study of Ross et al. (2016), assessing durability of psilocybin’s effects approximately 3–4.5 years later. Of the original Ross et al. sample, all 16 participants still alive were contacted, and 15 completed longitudinal assessments at ~3.2 years and ~4.5 years post-treatment. No additional drug sessions were given; this was a naturalistic observation of lasting outcomes.
Sample: 15 patients.
Dosage: N/A
Key Findings:
– The reductions in anxiety, depression, hopelessness, and demoralization observed after psilocybin therapy were largely sustained at long-term follow-ups.
– At 4.5 years, an estimated 60–80% of participants still met criteria for clinically significant antidepressant or anxiolytic responses.
– Many participants reported the psilocybin session as among the most personally meaningful experiences of their lives, with 71–100% attributing positive life changes (improved well-being, life satisfaction, spiritual sustenance) to the therapy.
Implications: Suggests that a one-time psilocybin-assisted therapy can confer enduring relief from end-of-life psychiatric distress, although the authors caution that conclusions are limited by the parent trial’s cross-over design
Citation: Agin-Liebes, G. I., Malone, T., Yalch, M. M., Mennenga, S. E., Ponté, K. L., Guss, J., Bossis, A. P., Grigsby, J., Fischer, S., & Ross, S. (2020). Long-term follow-up of psilocybin-assisted psychotherapy for psychiatric and existential distress in patients with life-threatening cancer. Journal of psychopharmacology (Oxford, England), 34(2), 155–166. https://doi.org/10.1177/0269881119897615
Longitudinal experiences of Canadians receiving compassionate access to psilocybin-assisted psychotherapy
de la Salle, S., Kettner, H., Thibault Lévesque, J., Garel, N., Dames, S., Patchett-Marble, R., Rej, S., Gloeckler, S., Erritzoe, D., Carhart-Harris, R., & Greenway, K. T. (2024). Scientific reports.
Methodology: Prospective observational study of “compassionate use” psilocybin therapy in Canada, examining real-world outcomes for palliative patients. Participants completed surveys at baseline and at 2 weeks after a single psilocybin session (with an optional next-day check-in).
Sample: Eight patients (four females, Mage = 52.3 years, all with advanced cancer diagnoses) obtained legal exemptions (Section 56 in Canada) to undergo psilocybin-assisted psychotherapy in a clinical setting.
Dosage: All participants reported consuming the psilocybin in the form of psilocybin mushrooms or truffles (dried; 2/5 reported taking Golden Teacher [Psilocybe cubensis strain]; the other three reported not knowing). The majority reported taking only one dose ranging from 2.5 g (n = 1) to 5 g (n = 4) (one patient reported two doses over the course of the session as 3.33 and 1.66 doses, less than 1 h apart). Two participants consumed the psilocybin mushrooms/truffles whole, while the three others consumed it cooked or brewed into a tea.
Key Findings:
– At two-weeks post-session, there were significant improvements in anxiety and depression symptoms, pain, fear of COVID-19, quality of life, and spiritual well-being compared to baseline
– Importantly, attitudes toward death and desire for hastened death did not change, suggesting psilocybin eased distress without diminishing realistic outlooks on mortality.
– Most participants found the experience highly meaningful (albeit challenging) and their psychological well-being improved, except one patient who reported a substantial decline in well-being attributable to the session.
Implications: These real-world preliminary data (among the first collected outside of a formal trial) indicate that psilocybin-assisted psychotherapy can yield benefits in “real-world” palliative-care patients akin to those seen in controlled trials, while underscoring the need for ongoing monitoring and structured support as access expands.
Citation: de la Salle, S., Kettner, H., Thibault Lévesque, J., Garel, N., Dames, S., Patchett-Marble, R., Rej, S., Gloeckler, S., Erritzoe, D., Carhart-Harris, R., & Greenway, K. T. (2024). Longitudinal experiences of Canadians receiving compassionate access to psilocybin-assisted psychotherapy. Scientific reports, 14(1), 16524. https://doi.org/10.1038/s41598-024-66817-0
Psilocybin mushrooms for psychological and existential distress. Treatment for a patient with palliative lung cancer
Patchett-Marble, R., O’Sullivan, S., Tadwalkar, S., & Hapke, E. (2022). Canadian Family Physician.
Methodology: With special authorization, the patient underwent one psilocybin therapy session facilitated by two family physicians in a community setting.
Sample: A woman in her 50s with advanced lung cancer suffering from severe existential and psychological distress despite standard palliative care.
Dosage: 5g of dried psilocybin mushrooms (steeped as a tea).
Key Findings:
– Consistent with clinical trial observations, this single session triggered a profound mystical-type experience, which the patient later described as “the single-most personally meaningful experience of her life.”
– She experienced an immediate transformation with substantial and sustained improvement in her anxiety, mood, and overall quality of life following the session.
– Importantly, no adverse physical or psychiatric events were noted.
Implications: This case underscores that, even in a non-research, compassionate-use context, psilocybin therapy can lead to rapid and durable relief of end-of-life existential distress, in line with outcomes reported in larger trials.
Citation: Patchett-Marble, R., O’Sullivan, S., Tadwalkar, S., & Hapke, E. (2022). Psilocybin mushrooms for psychological and existential distress. Canadian Family Physician, 68(11), 823-827. https://doi.org/10.46747/cfp.6811823
HOPE: A Pilot Study of Psilocybin Enhanced Group Psychotherapy in Patients With Cancer
Lewis, B. R., Garland, E. L., Byrne, K., Durns, T., Hendrick, J., Beck, A., & Thielking, P. (2023). Journal of pain and symptom management.
Methodology: An open-label pilot trial exploring psilocybin in a group therapy format to treat demoralization and depression in cancer patients. Therapy was delivered partly in group sessions: each cohort of four patients met for three preparatory therapy sessions, then received a single high dose (25 mg) of psilocybin simultaneously in a group setting, facilitated by therapists (one therapist per patient present). After the dosing day, three group integration sessions were held. Outcomes (depression, anxiety, etc.) were measured at baseline, 2 weeks, and 26 weeks post-treatment.
Sample: 12 adults with cancer and DSM-5 depressive disorders (major depression or adjustment disorder).
Dosage: 25mg of psilocybin
Key Findings:
– All 12 participants completed the intervention, and no serious adverse events or safety issues were attributable to psilocybin.
– Depression symptoms improved markedly: the mean clinician-rated depression score (HAM-D) fell from 21.5 at baseline to 10.1 at 2 weeks, and 14.8 at 26 weeks (both timepoints showed statistically significant improvement).
– At 2 weeks post-session, 6 of 12 patients (50%) achieved clinical remission of depression (HAM-D <7).
– Some relapse of depressive symptoms occurred by 26 weeks, but scores remained significantly better than baseline.
Implications: The pilot demonstrated feasibility and potential efficacy of group-administered psilocybin – showing rapid antidepressant responses similar in magnitude to individual therapy trials. The group modality also reduced total therapist hours per patient, hinting at greater scalability. Authors concluded that psilocybin-assisted group therapy appears safe, acceptable, and worthy of further study to improve end-of-life mental health in a resource-efficient way
Citation: Lewis, B. R., Garland, E. L., Byrne, K., Durns, T., Hendrick, J., Beck, A., & Thielking, P. (2023). HOPE: A Pilot Study of Psilocybin Enhanced Group Psychotherapy in Patients With Cancer. Journal of pain and symptom management, 66(3), 258–269. https://doi.org/10.1016/j.jpainsymman.2023.06.006
Psilocybin-assisted group therapy in patients with cancer diagnosed with a major depressive disorder
Agrawal, M., Richards, W., Beaussant, Y., Shnayder, S., Ameli, R., Roddy, K., Stevens, N., Richards, B., Schor, N., Honstein, H., Jenkins, B., Bates, M., & Thambi, P. (2024). Cancer.
Methodology: Open-label phase II trial evaluating psilocybin therapy for major depression in cancer patients, delivered at a community oncology clinic. Each patient underwent a single 25 mg psilocybin session administered simultaneously to groups of 3–4 patients, with a hybrid support model: each participant had an individual therapist (one-to-one monitoring during the 4+ hour session) and additional group therapy elements before and after dosing. Outcomes tracked included depression severity (primary), anxiety, pain, demoralization, and disability, assessed up to 8 weeks post-treatment.
Sample: Thirty adult patients with cancer (various stages, both curable and incurable) and co-morbid major depressive disorder.
Dosage: 25mg of psilocybin
Key Findings:
– No psilocybin-related serious adverse events occurred; the treatment was well-tolerated, with only mild, expected side effects (e.g. transient nausea or headache) and no cases of study-related suicidality or medical complications.
– Depression outcomes were very promising: by 8 weeks after the session, depression severity (measured by QIDS/SR or a similar scale) dropped by an average of ~19 points from baseline, a robust improvement (p < 0.0001).
– 80% of participants met criteria for treatment response, and 50% achieved full remission of depression one week after psilocybin, an effect that was largely sustained at 8 weeks.
– Anxiety, demoralization, and other secondary measures also trended positively (as noted in text).
Implications: Psilocybin-assisted therapy given in small groups was feasible, safe, and showed strong signals of efficacy in alleviating depression and distress in cancer patients. The authors highlighted the novel format’s success in a community clinic setting, suggesting this could be an efficient model to extend psychedelic therapy to palliative care settings if validated by controlled trials.
Citation: Agrawal, M., Richards, W., Beaussant, Y., Shnayder, S., Ameli, R., Roddy, K., Stevens, N., Richards, B., Schor, N., Honstein, H., Jenkins, B., Bates, M., & Thambi, P. (2024). Psilocybin-assisted group therapy in patients with cancer diagnosed with a major depressive disorder. Cancer, 130(7), 1137–1146. https://doi.org/10.1002/cncr.35010
Patient Experiences of Psilocybin-Assisted Psychotherapy: An Interpretative Phenomenological Analysis
Belser, A. B., Agin-Liebes, G., Swift, T. C., Terrana, S., Devenot, N., Friedman, H. L., Guss, J., Bossis, A., & Ross, S. (2017). Journal of Humanistic Psychology.
Methodology: Qualitative study (Interpretative Phenomenological Analysis) of patient experiences from a psilocybin trial. This was the first in-depth qualitative analysis of psilocybin therapy in cancer patients. Semi-structured interviews were conducted with patients who had clinically elevated anxiety due to cancer and who received a single moderate dose of psilocybin in a therapeutic trial. The interviews, focusing on how psilocybin affected patients’ psychology, were transcribed and analyzed by a team using interpretative phenomenological analysis (IPA) to extract common themes.
Sample: 13 adults (ages 22–69) who had clinically elevated anxiety due to cancer.
Dosage: Single moderate dose of psilocybin in a therapeutic trial.
Key Findings:
– The psychedelic experience catalyzed a range of meaningful psychological and spiritual insights for patients. The researchers identified multiple recurring themes across participants’ narratives, including “relational embeddedness” (enhanced sense of connection to others), emotional range (from challenging fear to sublime joy and love), the profound impact of music during the session, meaningful visions, revised life priorities, and even a desire by many to eventually repeat the experience.
– Patients commonly reported episodes of mystical or ineffable experience, feelings of transcendence and unity, as well as confronting transient psychological distress that transformed into catharsis or acceptance
– Importantly, some participants described lasting positive changes: improved relationships, forgiveness of self and others, and a greater sense of spiritual peace. The authors conclude that psilocybin-assisted psychotherapy was effective in helping patients cope with cancer-related distress, by facilitating emotionally intense but ultimately healing experiences that addressed existential fears.
– Anxiety, demoralization, and other secondary measures also trended positively (as noted in text).
Implications: This qualitative evidence supports the clinical results, illustrating how psilocybin experiences lead to reduced suffering (e.g. through greater acceptance, meaning, and emotional processing).
Citation: Belser, A. B., Agin-Liebes, G., Swift, T. C., Terrana, S., Devenot, N., Friedman, H. L., Guss, J., Bossis, A., & Ross, S. (2017). Patient experiences of psilocybin-assisted psychotherapy: An interpretative phenomenological analysis. Journal of Humanistic Psychology, 57(4), 354-388. https://doi.org/10.1177/0022167817706884
Cancer at the Dinner Table: Experiences of Psilocybin-Assisted Psychotherapy for the Treatment of Cancer-Related Distress
Swift, T. C., Belser, A. B., Agin-Liebes, G., Devenot, N., Terrana, S., Friedman, H. L., Guss, J., Bossis, A. P., & Ross, S. (2017). Journal of Humanistic Psychology.
Methodology: Qualitative analysis focusing on existential themes. 13 cancer patients (from the same NYU trial) to specifically explore how psilocybin sessions affected their perceptions of cancer, mortality, and life’s meaning.
Sample: 13 cancer patients (from the same Ross et al., 2016 trial) to specifically explore how psilocybin sessions affected their perceptions of cancer, mortality, and life’s meaning.
Dosage: 0.3 mg/kg of psilocybin
Key Findings:
– Participants initially described the psilocybin session as an intense, immersive – sometimes emotionally difficult – experience, but one that led to pivotal insights.
– Nearly all patients reported that the journey helped them achieve “reconciliation with death” – they faced and ultimately found acceptance of their mortality.
– Patients spoke of acknowledging cancer’s place in their life story (rather than only seeing it as an enemy), and many experienced an “emotional uncoupling” from the grip of cancer – a release of fear and trauma associated with the illness.
– Several also recounted encounters with what they interpreted as spiritual or divine figures, and made spiritual or religious meaning out of their trip.
– Common outcomes included a renewed sense of connection to life, a reclaiming of presence in the here-and-now instead of being overwhelmed by illness, and greater confidence in facing the possibility of recurrence or death.
Implications: In essence, psilocybin enabled patients to reframe their relationship with their illness and mortality in a more accepting and life-affirming way. The authors suggest these qualitative outcomes (confronting and reducing death anxiety, finding peace with one’s fate) underlie the clinical improvements, highlighting psilocybin’s unique capacity to address existential distress in terminal illness.
Citation: Swift, T. C., Belser, A. B., Agin-Liebes, G., Devenot, N., Terrana, S., Friedman, H. L., Guss, J., Bossis, A. P., & Ross, S. (2017). Cancer at the dinner table: Experiences of psilocybin-assisted psychotherapy for the treatment of cancer-related distress. Journal of Humanistic Psychology, 57(5), 488-519. https://doi.org/10.1177/0022167817715966
Individual Experiences in Four Cancer Patients Following Psilocybin-Assisted Psychotherapy
Malone, T. C., Mennenga, S. E., Guss, J., Podrebarac, S. K., Owens, L. T., Bossis, A. P., Belser, A. B., Agin-Liebes, G., Bogenschutz, M. P., & Ross, S. (2018). Frontiers in pharmacology.
Methodology: Case series of four individual patients from a psilocybin trial, providing detailed narrative “portraits” of their therapeutic journeys. Rather than aggregate data, this report presents in-depth case studies to illustrate the range of subjective experiences and outcomes. Participants had completed psilocybin therapy and showed significant improvements, yet each processed the experience differently. The authors integrated quantitative measures (mood, anxiety, quality-of-life scales over time) with qualitative materials (interview excerpts, patients’ written narratives, and therapists’ notes) to chronicle each person’s course.
Sample: Four participants from the Ross et al. (2016) trial.
Dosage: 0.3 mg/kg of psilocybin
Key Findings:
– Although every patient’s psilocybin session was highly personal and unique, there were notable thematic commonalities across these stories.
– All four patients experienced sequences of psychological insight that extended far beyond their cancer diagnosis, frequently touching on themes of self-compassion and self-forgiveness, feelings of love, confronting past traumas, and ultimately acceptance of death.
– For example, one patient described a vision of attending her own funeral and came away with a profound peace about dying; another revisited painful life memories and emerged with newfound self-compassion. Despite the different content of each vision, all patients saw a reduction in existential distress and improvement in their emotional well-being following the session.
– The authors emphasize the “personalized nature” of the psychedelic experience: each patient’s encounter seemed tailored to their most pressing psychological needs (be it resolving trauma, mending relationships, or accepting mortality).
Implications: These narrative cases demonstrate how psilocybin therapy can flexibly address individual end-of-life struggles, while still consistently eliciting relief and peace in patients facing death. Such detailed cases complement group findings by showing how psilocybin catalyzes meaningful therapeutic processes on a person-by-person basis.
Citation: Malone, T. C., Mennenga, S. E., Guss, J., Podrebarac, S. K., Owens, L. T., Bossis, A. P., Belser, A. B., Agin-Liebes, G., Bogenschutz, M. P., & Ross, S. (2018). Individual Experiences in Four Cancer Patients Following Psilocybin-Assisted Psychotherapy. Frontiers in pharmacology, 9, 256. https://doi.org/10.3389/fphar.2018.00256