Cannabinoids fail to reduce opioid use in cancer pain

Opioids are the mainstay of cancer-related pain management but are limited by adverse effects and clinical complexity. Cannabinoids have been proposed as adjunctive, opioid-sparing agents, yet their impact on opioid consumption in cancer patients remains uncertain. This systematic review and meta-analysis was conducted according to PRISMA 2020 guidelines and registered in PROSPERO (CRD420251175971). Randomized and nonrandomized clinical studies involving adult cancer patients receiving opioids for pain and treated with cannabinoids were included. Outcomes comprised total opioid consumption, maintenance/background opioid dose, and breakthrough/rescue opioid use. Placebo-controlled comparisons were analyzed separately from within-group baseline changes. Risk of bias was assessed using RoB 2 and ROBINS-I, and certainty of evidence using GRADE. Fifteen studies met inclusion criteria, with ten eligible for meta-analysis. Placebo-controlled analyses showed no significant differences between cannabinoids and placebo for total, maintenance, or breakthrough opioid use. Baseline-change analyses demonstrated heterogeneous and formulation-dependent effects, with modest reductions in maintenance opioid dose observed primarily in THC-predominant regimens, driven by isolated studies. Overall certainty of evidence was low due to heterogeneity and methodological limitations. Cannabinoids are not associated with consistent or clinically meaningful opioid-sparing effects in cancer pain under controlled conditions. Observed benefits in uncontrolled analyses are variable and not reliably reproduced. Cannabinoids should not be considered a dependable opioid-sparing strategy in cancer pain management.