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.

People living with cancer (PLWC) often face profound existential distress that is insufficiently addressed by conventional psychosocial supports. This qualitative study explored PLWC’s attitudes, beliefs, and experiences regarding psychedelic-assisted therapy (PAT) as a novel approach to addressing psychosocial suffering, particularly existential distress. Fifteen participants with varying cancer types and stages were recruited from a national survey. Semi-structured interviews were analyzed using reflexive thematic analysis informed by the Theory of Planned Behavior. Four key themes were identified: (1) Cautious Optimism and Substance-Specific Attitudes Toward Psychedelics reflected varied knowledge, openness, and perceptions of specific agents; (2) Relational and Societal Influences: Stigma, Support, and Cultural Framing; (3) Structural and Systemic Barriers: Cost, Legality, Provider Attitudes, and Unequal Access; and (4) Cancer Context and Psychosocial Needs: Seeking Relief from Existential and Emotional Distress captured the emotional, spiritual, and existential dimensions of living with and beyond cancer. Participants expressed cautious optimism about PAT, driven by unmet needs in conventional care, particularly after active treatment and at advanced stages of cancer, where existential and spiritual concerns often go unaddressed. PAT was seen as a potential adjunct that could meaningfully engage with suffering beyond symptom management. However, concerns about safety, access, and stigma underscore the need for culturally responsive, patient-informed, and equity-focused implementation strategies. Integrating PAT into oncology will require dismantling structural barriers and shifting toward a model of care that embraces the full human experience of serious illness.

Background: Healthcare providers’ (HCPs) perspectives on psychedelic-assisted therapy (PAT) are critical to clinical integration but remain underexplored in Canadian palliative and oncology contexts. This study examines HCP attitudes toward ketamine, psilocybin, and MDMA, and the systemic and ethical factors influencing implementation. Methods: An exploratory qualitative study using semi-structured interviews was conducted with 12 HCPs across Canada. Interviews explored attitudes, perceived barriers, and implementation considerations. Data were analyzed using thematic analysis and interpreted through the Theory of Planned Behaviour (TPB) to examine how attitudes, subjective norms, and perceived behavioural control shape clinical integration. Results: Attitudes toward PAT ranged from caution to advocacy, with neutral-to-cautious positions predominating. Ketamine was pragmatically accepted for rapid efficacy but raised concerns regarding commercialization and misuse. Psilocybin elicited mixed views, particularly in relation to end-of-life existential distress. MDMA was considered promising for trauma-related indications but was constrained by neurotoxicity concerns and regulatory barriers. Subjective norms were shaped by stigma, media narratives, and institutional culture, while perceived behavioural control was limited by restrictive policies, infrastructure gaps, and funding inequities. An ethical tension emerged between access to medical assistance in dying (MAiD) and restrictions on PAT in end-of-life care, highlighting perceived policy inconsistencies. Conclusion: Participants expressed a range of attitudes toward PAT, from caution to advocacy, alongside substantial ethical, regulatory, and systemic constraints to clinical integration. A notable ethical tension emerged between MAiD accessibility and PAT restrictions in end-of-life contexts, reflecting broader questions about Canadian health policy. Participants emphasized the need for substance-specific guidelines, interdisciplinary education, and evidence-informed regulatory reform to guide future clinical consideration of PAT.