How ABCB1 Polymorphisms Could Predict Nabiximols Response in MS Spasticity
Imagine living with a condition that turns your muscles into a battlefield—rigid, painful, and unrelenting. For many people with Multiple Sclerosis (MS), spasticity is exactly that: a daily struggle. While medications like nabiximols (a cannabis-derived treatment known commercially as Sativex®) offer relief to some, about 30–40% of patients see little benefit. But what if your DNA held the secret to knowing whether this treatment would work for you?
A recent study by Gemma et al. (2025) offers a compelling glimpse into that future. The researchers suggest that specific genetic variants—particularly in the ABCB1 gene—could be key to predicting how patients respond to nabiximols. This finding opens the door to a more personalized, gene-guided approach in MS treatment.
Why Nabiximols, and Why Doesn’t It Work for Everyone?
Nabiximols is a mouth spray that combines THC (tetrahydrocannabinol) and CBD (cannabidiol)—two well-known cannabinoids from the cannabis plant. It's approved for the treatment of moderate-to-severe MS-related spasticity. While the formulation targets cannabinoid receptors in the brain to reduce muscle stiffness, not all patients benefit equally.
The reason? Likely genetics. Just as your genes influence how you metabolize caffeine or alcohol, they also affect how your body responds to cannabis-based treatments.
What Did the Study Find?
The study analyzed 45 MS patients treated with nabiximols. After four weeks of treatment:
29 were classified as responders (with ≥30% reduction in muscle spasticity on a standardized scale).
16 were non-responders.
The researchers examined seven specific genetic variants (SNPs) across genes known to be involved in cannabinoid metabolism, transport, and receptor binding—including CNR1, CNR2, CYP2C9, CYP2C19, and most crucially, ABCB1.
Two standout findings emerged:
ABCB1 1236C>T (rs1128503)
38% of responders had the T/T genotype.
0% of non-responders had the T/T genotype.
Odds ratio: 20.5 – a striking indicator of predictive power.
ABCB1 3435A>T (rs1045642)
48% of responders had the T/T genotype.
Again, none of the non-responders did.
Odds ratio: 30.9 – even stronger predictive value.
These T alleles are associated with reduced P-glycoprotein activity, a transporter that normally pumps substances out of the brain. Reduced activity could mean higher concentrations of nabiximols in the brain, enhancing its therapeutic effects.
What Didn’t Matter?
Interestingly, variations in:
Cannabinoid receptor genes (CNR1, CNR2),
Metabolic enzymes (CYP2C9, CYP2C19),
...did not show any meaningful connection to treatment response in this study. This shifts the spotlight firmly onto the ABCB1 gene.
Why This Matters
This research is among the first to suggest that ABCB1 polymorphisms may be used as biomarkers to predict which MS patients are more likely to benefit from nabiximols.
If validated in larger, prospective studies, such genetic markers could:
Reduce the trial-and-error in prescribing nabiximols.
Spare non-responders from unnecessary side effects.
Enable precision medicine in managing MS-related spasticity.
Caveats and Next Steps
The study had a relatively small sample size (n=45) and a retrospective design, meaning more robust, prospective trials are needed before this approach could be used clinically. Still, the clear genetic signal in this exploratory study is promising.
Future studies might explore:
Whether these findings apply to other cannabinoid-based therapies.
How ABCB1 interacts with other genes or environmental factors.
The role of blood-brain barrier permeability in modulating treatment outcomes.
Final Thoughts
This study exemplifies how understanding our genetic blueprint can revolutionize treatment. By tailoring medications to genetic profiles, we edge closer to a future where therapies are not just effective—but personalized. For the MS community, this could mean better management of spasticity and, importantly, a better quality of life.
Disclaimer: This blog post is based on the provided research article and is intended for informational purposes only. It is not intended to provide medical advice. Please consult with a healthcare professional for any health concerns.
References:
Gemma A, et al. ABCB1 Gene Polymorphisms Are Associated with Clinical Response to Nabiximols in Patients with Multiple Sclerosis-Related Spasticity. medRxiv, 2025.
