Endocannabinoid System Clinical Research: Topical Cannabis Balm Efficacy in AIMSS Treatment
Clinical Takeaway
In this randomized trial, topical cannabis balms were evaluated for feasibility and tolerability in postmenopausal breast cancer patients experiencing joint pain and stiffness from aromatase inhibitor therapy. The study focused on whether cannabinoid-based topical products could be a practical and well-tolerated option for managing AIMSS, a condition that causes many women to discontinue a proven cancer treatment. Results provide early clinical data on the local application of cannabinoids as a potential strategy to improve adherence to aromatase inhibitor therapy.
#23 A Randomized, Open-Label Trial to Assess Feasibility and Tolerability of Topical Cannabis Balms for the Treatment of Aromatase Inhibitor-Associated Musculoskeletal Syndrome (AIMSS).
Citation: Zylla Dylan et al.. A Randomized, Open-Label Trial to Assess Feasibility and Tolerability of Topical Cannabis Balms for the Treatment of Aromatase Inhibitor-Associated Musculoskeletal Syndrome (AIMSS).. Cannabis and cannabinoid research. 2026. PMID: 41467893.
Design: 5 Journal: 1 N: 0 Recency: 3 Pop: 2 Human: 1 Risk: -2
- Preclinical only
Methodological Considerations:
- Open-label design — placebo effect not excluded
Abstract: INTRODUCTION: Aromatase inhibitors (AIs) are commonly used for postmenopausal women with hormone receptor-positive breast cancer. Nearly two-thirds of women on AIs have arthralgias, joint stiffness, and/or bone pains referred to as aromatase inhibitor-induced musculoskeletal syndrome (AIMSS), leading to poor adherence. Preclinical and clinical data suggest topical cannabinoids can reduce inflammation in arthritis. MATERIALS AND METHODS: We conducted a randomized trial assessing feasibility, tolerability, and preliminary efficacy of topical cannabis for women with stage 1-3 breast cancer experiencing AIMSS. Women were randomized 1:1 to cannabidiol (CBD) vs. delta-9-tetrahydrocannabinol (THC) balms. The balm was applied three times daily to hands for 2 weeks, followed by a 2-week extension with the balm of their choice. Modified Score for the Assessment and Quantification of Chronic Rheumatoid Affectations of the Hands (M-SACRAH), brief pain inventory, and skin toxicity measures were captured weekly. RESULTS: A total of 21 women completed the study over 14 months. The mean age was 54, 86% White, 43% received adjuvant chemotherapy, and 48% reported no lifetime cannabis use. Compliance was high, with 71% continuing an additional 2 weeks and 86% of weekly surveys completed. We found 86% of participants reported improvement in M-SACRAH from baseline to week 2 with a higher percentage of the THC balm group reporting a >50% improvement (50% vs. 18%). Minor skin irritation was reported by 24%, and one patient discontinued balm due to “greasy” texture. CONCLUSIONS: Conducting a randomized trial of topical cannabis using state-approved dispensaries is feasible. Both THC and CBD balms are well tolerated. Placebo-controlled trials are needed to determine if balms can reduce AIMSS severity in breast cancer survivors.
What This Study Teaches Us
In a small open-label trial, topical cannabis balms (both THC and CBD) were well tolerated in women with aromatase inhibitor-related joint and bone pain, with 86% reporting some improvement over 2 weeks and THC showing numerically higher response rates than CBD. The trial demonstrates feasibility of conducting cannabis studies through regulated dispensaries, but cannot yet claim efficacy without placebo control.
Why This Matters Clinically
AIMSS causes up to two-thirds of postmenopausal breast cancer patients on aromatase inhibitors to skip or stop doses, compromising cancer outcomes. If topical cannabinoids prove effective, they could offer a non-systemic option for a common, adherence-threatening side effect, but we need rigorous placebo-controlled data before recommending it in practice.
Study Snapshot
| Study Design | Randomized open-label trial (1:1 allocation) with 2-week intervention followed by 2-week extension phase |
| Population | 21 women with stage 1-3 breast cancer on aromatase inhibitors experiencing AIMSS. Mean age 54, 86% White, 43% prior adjuvant chemotherapy, 48% no lifetime cannabis use |
| Intervention | Topical cannabis balm applied three times daily to hands for 2 weeks (CBD vs THC), followed by 2-week extension with choice of balm |
| Primary Outcome | Feasibility, tolerability, and preliminary efficacy measured by modified M-SACRAH hand assessment, brief pain inventory, and skin toxicity |
| Key Result | 86% reported M-SACRAH improvement baseline to week 2; 50% of THC group achieved >50% improvement vs 18% of CBD group. 71% enrolled in extension phase. Minor skin irritation in 24%; one dropout due to texture |
Where This Paper Deserves Skepticism
This is a very small, open-label trial without placebo control, making it impossible to separate active drug effect from expectation and natural variation. The 14-month enrollment window for only 21 participants suggests slow recruitment, and the abstract does not disclose funding source, potential conflicts, or whether baseline characteristics differed between arms. The short 2-week window cannot speak to durability or long-term safety. High attrition risk after week 2 (only 71% continued) hints at limited real-world enthusiasm despite reported improvements.
Dr. Caplan’s Take
I find this study useful as a proof-of-concept for conducting cannabis research within state regulatory frameworks, but not yet as evidence for prescribing topical cannabinoids for AIMSS. The data suggest tolerability and that patients can and will apply these products consistently, which is valuable. However, without a placebo arm, the 86% improvement rate is largely uninterpretable. Open-label cannabis trials are particularly vulnerable to expectancy effects given the visibility and strong patient beliefs about cannabis. The numerical advantage of THC over CBD is intriguing but underpowered to claim. I’d watch for a well-designed placebo-controlled follow-up.
Clinical Bottom Line
Topical cannabis balms are feasible to study and appear safe for women with AIMSS, but this open-label trial cannot demonstrate efficacy. A placebo-controlled trial is the necessary next step before considering this an evidence-based option for aromatase inhibitor-related pain.
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