Only Five Trials Found: Cannabinoids for Post-Surgery Pain Remain an Open Question

A new systematic review confirms the evidence base is too thin and too heterogeneous to draw conclusions about whether cannabis-based medicines help after surgery, finding only five eligible randomized controlled trials worldwide and contradictory results that preclude any quantitative synthesis or clinical recommendation.

Why This Matters

The opioid crisis has made the search for effective non-opioid analgesics one of the most urgent priorities in perioperative medicine. Cannabinoids are among the most frequently discussed alternatives, and patients increasingly ask about them before and after surgical procedures. Yet the gap between public enthusiasm and rigorous clinical evidence is enormous. This review arrives at a moment when clinicians need clarity about what the controlled trial data actually show, and the answer turns out to be that they show almost nothing at all.

Clinical Summary

Acute postoperative pain remains one of the most common and consequential clinical challenges in surgery, and inadequately managed pain drives prolonged opioid use, delayed recovery, and patient dissatisfaction. Cannabinoids, both natural and synthetic, interact with CB1 and CB2 receptors in pain-processing pathways and have shown analgesic potential in preclinical models and some chronic pain contexts. This systematic review, published in the European Journal of Pain in 2025 by researchers affiliated with Universidad El Bosque in Colombia, attempted to synthesize all available RCT evidence on cannabinoid use specifically for acute postoperative pain. The authors followed PRISMA and Cochrane guidelines, searched PubMed, Embase, Cochrane, LILACS, and secondary databases without language or date restrictions, and used blinded extraction with group reconciliation.

Of 62 articles initially identified, only five RCTs met inclusion criteria, an attrition rate that itself underscores the scarcity of controlled data. The included trials produced contradictory results: no consistent signal of benefit or harm emerged for pain intensity measured by visual analogue scale, rescue analgesic consumption, or adverse events. Methodological heterogeneity across the five studies, including disparate cannabinoid types, dosing regimens, surgical populations, and outcome definitions, was so pronounced that quantitative meta-analytic pooling proved impossible. Three of the five studies were rated low risk of bias, and four showed high inter-observer agreement, suggesting the quality problem is one of volume and standardization rather than individual study integrity alone. The authors conclude that larger, methodologically harmonized trials are essential before any clinical recommendations can be made.

Dr. Caplan’s Take

This review is honest about what it found, and what it found is essentially a void. Five RCTs, contradictory results, no pooling possible. That is the state of the evidence for cannabinoids in acute postoperative pain. When patients preparing for surgery ask me whether cannabis products might reduce their need for opioids afterward, I have to tell them that the clinical trial data simply do not exist in sufficient quantity or quality to answer that question. The mechanistic plausibility is real, but plausibility is not proof, and the gap between the two is particularly dangerous in a space where marketing often substitutes for evidence.

In practice, I do not recommend cannabinoid products as a substitute for or adjunct to standard perioperative analgesia. What I do is ensure patients have access to a well-designed multimodal pain management plan that uses interventions with established efficacy. If a patient is already using cannabis and is scheduled for surgery, I discuss potential interactions with anesthetics and analgesics, ensure their surgical team is informed, and focus on evidence-based optimization. That is the responsible approach until the trials this review calls for are actually conducted.

Clinical Perspective

This review sits very early in the research arc for cannabinoids in postoperative analgesia. It confirms that the field has not yet generated enough standardized RCT data to support even a tentative directional conclusion. The contradictory findings across the five included trials mean that clinicians cannot responsibly cite this body of evidence either for or against cannabinoid use in this setting. The review’s most valuable contribution is its mapping of specific methodological gaps: inconsistent cannabinoid preparations, variable dosing, non-standardized outcome measures, and heterogeneous surgical populations. Until future trials address these issues systematically, patient-facing recommendations should not reference cannabinoids as having demonstrated postoperative analgesic efficacy.

From a pharmacological standpoint, clinicians should be aware that cannabinoids can interact with anesthetic agents, affect cytochrome P450 metabolism relevant to many perioperative drugs, and may alter hemodynamic stability. Patients using cannabinoids preoperatively may have altered tolerance to sedatives and analgesics. The safety profile in the acute surgical context remains poorly characterized. One concrete recommendation clinicians can implement now is to routinely screen for cannabinoid use during preoperative assessment and document it, ensuring the anesthesia and surgical teams can adjust their plans accordingly rather than encountering unexpected pharmacological variables intraoperatively.

Study at a Glance

Study Type

Qualitative systematic review (no meta-analytic pooling performed despite title)

Population

Adults experiencing acute postoperative pain (specific surgical contexts not detailed in extracted text)

Intervention

Natural or synthetic cannabinoids

Comparator

Placebo or conventional analgesics

Primary Outcomes

Pain intensity (VAS), rescue analgesic use, adverse events

Sample Size

5 RCTs included from 62 screened articles (individual trial sizes not reported in extracted text)

Journal

European Journal of Pain

Year

2025

DOI or PMID

Not available in extracted text

Funding Source

Universidad El Bosque (Colombia), Agreement No. 17259

What Kind of Evidence Is This

This is a qualitative systematic review of randomized controlled trials conducted according to PRISMA and Cochrane standards, though its title includes the term “meta-analysis.” Because the five included studies were too heterogeneous to pool statistically, no quantitative synthesis was performed. The single most important inference constraint is that the review can only describe the existing landscape of trial evidence narratively; it cannot generate effect size estimates, confidence intervals, or any statistical measure of cannabinoid efficacy or safety in this population.

How This Fits With the Broader Literature

The finding of insufficient evidence is consistent with earlier assessments. The 2018 National Academies of Sciences report on cannabis therapeutics noted limited evidence for acute pain specifically, and systematic reviews of cannabinoids in chronic pain contexts, such as the 2018 Cochrane review by Mücke and colleagues, have similarly emphasized heterogeneity and small study numbers as persistent obstacles. This review extends those findings by confirming that the acute postoperative niche remains even less developed than the chronic pain literature. It challenges the assumption, sometimes implied in clinical commentary, that cannabinoid analgesic potential demonstrated in chronic conditions can be extrapolated to the acute surgical setting without dedicated trial evidence.

Common Misreadings

The most likely overinterpretation is treating this review as a “meta-analysis that found no benefit,” which would imply a quantitative conclusion of inefficacy. That is not what occurred. No statistical pooling was performed, so no null result was generated. The review found that the question is unanswerable with current data, which is fundamentally different from finding that cannabinoids do not work. Equally, the title’s inclusion of “meta-analysis” may lead readers to assign this paper more evidential weight than a qualitative narrative of five heterogeneous trials warrants. Clinicians should cite this review as evidence of an evidence gap, not as evidence of absence of effect.

Bottom Line

This systematic review establishes that the controlled trial evidence for cannabinoids in acute postoperative pain is critically sparse and internally contradictory. It does not establish efficacy, inefficacy, or a reliable safety profile. Its principal contribution is a clear articulation of the methodological standards future trials must meet. For now, cannabinoids cannot be recommended as part of evidence-based postoperative analgesia, and clinicians should focus on multimodal strategies with established efficacy while awaiting adequately powered and standardized research.

References

1. Systematic review of cannabinoids for acute postoperative pain. European Journal of Pain, 2025. Funded by Universidad El Bosque, Agreement No. 17259. (Full citation details including DOI not available in extracted text.)
2. National Academies of Sciences, Engineering, and Medicine. The Health Effects of Cannabis and Cannabinoids: The Current State of Evidence and Recommendations for Research. Washington, DC: The National Academies Press; 2017. DOI: 10.17226/24625.
3. Mücke M, Phillips T, Radbruch L, Petzke F, Häuser W. Cannabis-based medicines for chronic neuropathic pain in adults. Cochrane Database of Systematic Reviews. 2018;(3):CD012182. DOI: 10.1002/14651858.CD012182.pub2.