Clinical Takeaway
Researchers attempted a randomized controlled trial comparing inhaled THC-dominant cannabis, oral cannabinoid oil, and placebo for endometriosis pain, but faced significant feasibility challenges in completing the study. While many patients with endometriosis already use cannabis on their own for symptom relief, rigorous clinical evidence confirming its effectiveness remains lacking. This trial highlights the real-world difficulties of conducting placebo-controlled cannabis research in this population.
#21 Challenges in conducting a feasibility randomized controlled trial of medicinal cannabis for endometriosis pain in Australia.
Citation: Chesterman Susan et al.. Challenges in conducting a feasibility randomized controlled trial of medicinal cannabis for endometriosis pain in Australia.. Complementary therapies in clinical practice. 2025. PMID: 41005282.
Design: 5 Journal: 0 N: 0 Recency: 2 Pop: 2 Human: 1 Risk: 0
Endometriosis patients currently use cannabis off-label for symptom management without established efficacy data, making this feasibility study essential for designing future definitive trials that could provide evidence-based alternatives to conventional analgesics. The study’s evaluation of safety and acceptability of different cannabis delivery routes addresses a critical gap in understanding whether cannabis represents a viable therapeutic option for this chronic pain condition where current treatments are frequently inadequate. Successful completion of this feasibility work is necessary to inform whether a larger, adequately powered RCT can proceed to generate the clinical evidence needed for potential regulatory consideration of cannabis-based medicines in endometriosis management.
Abstract: BACKGROUND AND PURPOSE: People with endometriosis report consuming cannabis to manage their endometriosis symptoms, however, its efficacy has not been established in clinical studies. This study aimed to determine the feasibility, acceptability, and safety of two different medicinal cannabis interventions against placebo in people with endometriosis. MATERIALS AND METHODS: A three-armed randomised controlled trial was conducted, comparing the effects of using both inhaled medicinal cannabis using dried flower containing 16 % delta-9-tetrahydrocannabinol (THC) via vaporisation and an oral oil containing 100mg cannabidiol (CBD) per mL together, versus an oral CBD oil alone, versus a taste- and colour-matched placebo oil. The trial aimed to recruit 63 participants (21 per intervention group). Outcome measures included safety and the occurrence of adverse events, and the acceptability and feasibility of recruitment and retention. RESULTS: Overall, 12 participants were randomised to one of three groups, of whom seven withdrew from the study; four completed the study and one was lost to follow-up. Therefore, acceptability and feasibility of recruitment and retention was considered low. There were 10 adverse events reported (two unrelated to cannabis and eight possibly related to cannabis) and two serious adverse events reported (both unrelated to the intervention). CONCLUSION: Despite an urgent need for an evidence-based approach to using cannabis for endometriosis-related pain, our feasibility trial failed to recruit and retain the small intended sample. Failure of the trial was largely driven by two factors: the requirement to abstain from driving, and a high level of participant withdrawal.
🔬 This feasibility study addresses an important evidence gap by attempting to evaluate medicinal cannabis for endometriosis pain, a condition where patients report symptom relief but rigorous clinical data remain scarce. The authors’ focus on feasibility and safety parameters is prudent given the complexity of cannabis pharmacology, variable cannabinoid ratios across products, and the challenge of blinding in cannabis trials where participants often detect active versus placebo interventions. Key limitations to consider include the small sample size typical of feasibility studies, potential selection bias toward cannabis-experienced or cannabis-curious patients, and difficulty controlling for confounders such as concurrent pain medications, hormonal therapies, or non-pharmacological interventions that patients with endometriosis typically employ. Clinicians should view preliminary feasibility data as a necessary but insufficient foundation for clinical decision-making, and should counsel patients with endometriosis that while cannabis use for symptom relief is increasingly prevalent, evidence-based guidance remains limited and individualized discussion of risks, potential interactions, and legal status in