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.

The CAnadian Network for Psychedelic-Assisted Cancer Therapy (CAN-PACT) was launched in 2025 to address urgent gaps in supportive care for Canadians with cancer experiencing demoralization syndrome (loss of meaning, dysphoria, disheartenment, helplessness, a sense of failure) and related psychosocial distress. CAN-PACT has six major objectives: (1) to develop a national interdisciplinary research and practice network; (2) to set research priorities through structured stakeholder engagement; (3) to develop and provide PAT training and education for clinicians, researchers, and patients; (4) to pilot test the feasibility of intervention and assessment procedures; (5) to conduct a multi-center, randomized controlled trial of PAT for people with advanced cancer; and (6) to inform and influence healthcare policy on PAT in Canada. We discuss the background and need for PAT in cancer, describe challenges currently limiting its use, and outline CAN-PACT’s strategy for building capacity, generating Canadian evidence, and preparing the oncology healthcare environment for potential implementation. This manuscript presents a summary overview of CAN-PACT as a multi-objective research program; detailed protocols for each discrete study component will be published separately as the research program progresses. Through environmental scans, national engagement, targeted training, rigorous research, and ongoing collaboration with policymakers, CAN-PACT aims to enable equitable access to safe, evidence-based PAT for people with advanced cancer in Canada’s publicly funded cancer centers.