This systematic review and meta-analysis evaluates (1) the effectiveness of psychedelic-assisted therapy (PAT) using psilocybin and ketamine for psychosocial symptoms in adults with cancer, (2) contextualizes findings with non-randomized and exploratory studies of other psychedelics, and (3) examines the role of therapeutic frameworks in shaping outcomes. We searched PubMed, Cochrane Library, PsycINFO, and EMBASE (2000–2024) for randomized controlled trials (RCTs) and non-randomized studies investigating psychedelic agents in cancer populations. Meta-analyses pooled RCTs of psilocybin or ketamine using random-effects models. Non-randomized studies were synthesized narratively. Risk of bias and evidence certainty were assessed via Cochrane ROB 2.0, NIH Before–After tool, and GRADE. Eleven placebo-controlled RCTs and four single open-label studies were included. Meta-analysis of four ketamine RCTs (n = 354) showed large, rapid effects on depression/anxiety (Hedges’ g = −1.37, 95% CI: −2.66 to −0.08; I² = 92%). Three psilocybin RCTs (n = 101) showed a large effect of psilocybin on alleviating depression (Hedges’ g = −3.13, 95% CI: −10.04 to 3.77; I² = 95%). MDMA and LSD trials suggested promise but lacked rigor. PAT may offer meaningful relief for cancer-related distress, though effects vary by therapeutic model and context. Oncology-specific trials are needed to standardize and scale for implementation.

Background: Survivors of cancer experience chronic gastrointestinal (GI) and psychosocial health symptoms and reduced gut microbial diversity. This may compromise their long-term health and wellbeing. No studies have investigated probiotics for managing both GI and psychosocial symptoms together, or their effects on the composition of the gut microbiota in post-treatment cancer survivors. Aims: To investigate the effects of a probiotic vs. placebo on (i) abdominal pain and depressive symptoms (primary outcomes); (ii) (a) GI (i.e., gas/bloating, diarrhea, and constipation), and psychosocial (i.e., anxiety, cognitive function, and fatigue) symptoms and (b) gut microbiota composition; and (iii) relationships between bacteria and GI and psychosocial symptoms. Methods: This double-blind, placebo-controlled, two-arm, randomized trial will recruit N = 66 participants allocated 1:1 to the probiotic or placebo group for a 12-week trial. Adult survivors diagnosed with a solid tumor or blood cancer who have completed chemotherapy within the last 5 years and show elevated GI or psychosocial symptoms will be included. The probiotic capsule contains a blend of Lacticaseibacillus rhamnosus, Lactobacillus helveticus, and Bifidobacterium animalis subsp. lactis strains, ingested orally once daily. Stool samples will be collected at baseline and week 12 and analyzed using 16S rRNA gene sequencing. GI and psychosocial surveys will be completed at baseline and at weeks 6 and 12. Descriptive statistics, frequencies, paired-samples t-tests, linear mixed models, and Spearman’s correlational analyses will be used. Conclusions: We explore a novel, microbiota-based intervention for chronic GI and psychosocial symptoms following cancer treatment. Our findings and commitment to person-centered knowledge translation via creating informational materials will enable people to make informed decisions about their health.