Investigating the therapeutic efficacy of psilocybin in advanced cancer patients: A comprehensive review and meta-analysis

Table 1 Search strings

Database	Search field	Search string
PubMed	Title, abstract	(psilocybin OR psilocybine OR hallucinogens OR serotonin agonists OR mushroom poisoning) AND (neoplasms OR cancer OR oncology OR neoplasm metastasis OR neoplasm staging OR neoplasm recurrence, local OR disease progression OR palliative care OR terminal care OR hospice care OR terminal illness OR quality of life)
CENTRAL	All fields	(psilocybin OR magic mushrooms) AND (cancer OR oncology) AND (advanced OR metastatic)

CENTRAL: Cochrane Central Register of Controlled Trials.

Table 2 Study descriptor table

Ref.	Publication year	Study design	Sample size	Mean age (SD)	Cancer diagnosis	Intervention details	Findings
Agin-Liebes et al[22]	2020	Randomized controlled trial	15, 40% Male	53 (15.5)	Various cancer types (breast, Reproductive, Lymphoma, and other types), stage I to IV	Psilocybin (0.3 mg/kg) on the first medication session followed by niacin (250 mg) on the second session (i.e. psilocybin-first group), or niacin (250 mg) on the first medication session followed by psilocybin (0.3 mg/kg) on the second session (i.e. niacin-first group)	Reductions in anxiety, depression, hopelessness, demoralization, and death anxiety were sustained at the first and second follow-ups. Participants overwhelmingly attributed positive life changes to the psilocybin-assisted therapy experience and rated it among the most personally meaningful and spiritually significant experiences of their lives
Griffiths et al[17]	2016	Randomized controlled trial	51, 51% Male	56.3	All 51 participants had a potentially life-threatening cancer diagnosis, with 65% having recurrent or metastatic disease. Types of cancer included breast (13 participants), upper aerodigestive (7), gastrointestinal (4), genitourinary (18), hematologic malignancies (8), and other (1)	The low-dose-1st group received the low dose (1 or 3 mg/70 kg) of psilocybin on the first session and the high dose on the second session, whereas the high-dose-1st group (22 or 30 mg/70 kg) received the high dose on the first session and the low dose on the second session	High-dose psilocybin produced large decreases in clinician- and self-rated measures of depressed mood and anxiety, along with increases in quality of life, life meaning, and optimism, and decreases in death anxiety. At 6-month follow-up, these changes were sustained, with about 80% of participants continuing to show clinically significant decreases in depressed mood and anxiety. Participants attributed improvements in attitudes about life/self, mood, relationships, and spirituality to the high-dose experience, with > 80% endorsing moderately or greater increased well-being/life satisfaction
Grob et al[16]	2011	Randomized controlled trial	12, 8% Male	Subjects ages ranged from 36 to 58 years	Primary cancers included breast cancer in 4 subjects, colon cancer in 3, ovarian cancer in 2, peritoneal cancer in 1, salivary gland cancer in 1, and multiple myeloma in 1. All subjects were in the advanced stages of their illness.	Each subject acted as his or her control and was provided 2 experimental treatment sessions spaced several weeks apart. They were informed that they would receive active psilocybin (0.2 mg/kg) on one occasion and the placebo, niacin (250 mg), on the other occasion. Psilocybin and placebo were administered in clear 00 capsules with corn starch and swallowed with 100 mL of water. A niacin placebo was chosen because it often induces a mild physiological reaction (e.g., flushing) without altering the psychological state. The order in which subjects received the 2 different treatments was randomized and known only by the research pharmacist. Treatment team personnel remained at the bedside with the subject for the entire 6-hour session	During treatment sessions, safe physiological and psychological reactions were observed. No significant adverse events related to psilocybin were reported. The State-Trait Anxiety Inventory showed a notable decrease in anxiety levels at 1 and 3 months post-treatment. Improvement in mood, as measured by the Beck Depression Inventory, became significant by the 6-month mark. Additionally, the Profile of Mood States indicated an enhancement in mood following psilocybin treatment, although this improvement did not quite reach statistical significance
Patchett-Marble et al[23]	2022	Observational study	1, 0% Male	54	Advanced lung cancer and substantial existential and psychological distress	The patient consumed 5 g of dried psilocybin mushrooms as a tea and was directed to go inward as she laid down with eye shades on and headphones playing gentle, guiding music. A quantity of 5 g was selected to approximate the dose of psilocybin used in clinical trials, based on reports of psilocybin concentrations in the Psilocybe cubensis mushrooms that she was to consume	In line with psilocybin administration in clinical studies, the single psilocybin session prompted a mystical encounter for the patient, which she later regarded as the most profoundly meaningful experience of her life. This encounter resulted in immediate, significant, and lasting enhancements in her well-being and overall quality of life
Ross et al[24]	2021	Randomized controlled trial	11, 36.4% Male	60.3 (7.1)	Patients were diagnosed with cancer at various sites, including breast, reproductive, lymphoma/leukemia, colon, and others, across stages I through IV	A controlled trial was designed to assess the efficacy of a single, moderate-to-high dose of oral psilocybin per session (0.3 mg/kg) vs a single-dose session of an orally administered active control (niacin 250 mg)	In individuals exhibiting elevated SI at baseline, PAP demonstrated significant reductions in suicidal ideation as early as 8 hours post-administration, persisting for 6.5 months thereafter. Additionally, PAP led to substantial decreases in Loss of Meaning from baseline, evident 2 weeks post-treatment and maintaining significance at 6.5 months, as well as at the 3.2 and 4.5-year follow-ups. Exploratory analyses support the hypothesis that PAP could serve as an effective intervention against suicidality following a cancer diagnosis, attributed to its positive effects on hopelessness, demoralization, and particularly its impact on meaning-making
Ross et al[25]	2016	Randomized controlled trial	29, 38% Male	56.28 (12.93)	Nearly two-thirds of participants (62%) had advanced cancers (stages III or IV). The types of cancer included: Breast or reproductive (59%); gastrointestinal (17%); hematologic (14%); and other (10%)	Psilocybin (0.3 mg/kg) first then niacin (250 mg) second, or niacin (250 mg) first then psilocybin (0.3 mg/kg) second	Psilocybin elicited immediate, significant, and enduring enhancements in anxiety and depression levels, alongside reductions in cancer-related demoralization and hopelessness. It also resulted in improved spiritual well-being and heightened quality of life. Follow-up assessments at 6.5 months revealed persistent anxiolytic and antidepressant effects, with approximately 60-80% of participants maintaining clinically significant reductions in depression or anxiety. Furthermore, sustained improvements were noted in existential distress and overall quality of life, along with a positive shift in attitudes towards death. It was observed that the therapeutic impact of psilocybin on anxiety and depression was mediated by the psilocybin-induced mystical experience
Swift et al[26]	2017	Qualitative interview study	13, 54% male	50 (15.77)	The distribution of cancer stages among participants is as follows: 31% were diagnosed with Stage I cancer, 15% with Stage II, 31% with Stage III, 15% with Stage IV, and 8% with other stages. Regarding the site of cancer, the breakdown is as follows: 23% of cases were in the breast, 15% in lymphoma, 31% in other locations, and 31% in the ovarian region	Participants were randomized to receive either: (1) Psilocybin (0.3 mg/kg) first and niacin (250 mg) second; or (2) niacin (250 mg) first and psilocybin (0.3 mg/kg) second	Participants recounted the intense and emotionally challenging impact of the psilocybin session, resulting in a profound acceptance of mortality, recognition of cancer's role in life, and a detachment from the emotional burden of the disease. Many participants interpreted their experiences through a spiritual or religious lens, finding that psilocybin therapy aided in reestablishing a deep connection with life, reclaiming a sense of presence, and fostering increased resilience against potential cancer relapse

SI: Suicidal ideation; PAP: Psilocybin-assisted psychotherapy.