Abstract
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; I(2) = 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; I(2) = 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.