CBD Relieved Facial Nerve Pain More Consistently Than Standard Treatment in Both Male and Female Rats | Research

The takeaway

In a trigeminal neuralgia rat model, CBD reduced facial pain in both sexes without affecting movement — unlike carbamazepine, the standard treatment, which showed sex-dependent efficacy and impaired locomotion.

Pain medicine specialists, neurologists treating trigeminal neuralgia, and researchers studying sex differences in pain treatment.

What the researchers found

CBD demonstrated potent antinociceptive effects in both male and female rats with trigeminal neuralgia, without affecting locomotor activity. Carbamazepine showed sex-dependent efficacy. CBD's mechanisms included inhibiting Fos-B expression, reducing superoxide oxidation, and modulating microglia and astrocytes in pain pathways, with some sex-dependent regional differences.

Why it matters

Trigeminal neuralgia is one of the most painful conditions known, and the standard treatment (carbamazepine) has significant side effects and doesn't work equally well for everyone. CBD's consistent efficacy across sexes and lack of motor impairment make it a promising alternative worth investigating in clinical trials.

The numbers in context

CBD reduced mechanical allodynia in both sexes. Carbamazepine showed sex-dependent efficacy. CBD inhibited Fos-B in Sp5c (both sexes) and vlPAG (males only). CBD prevented superoxide oxidation in vlPAG in both sexes. No locomotor impairment with CBD (unlike carbamazepine).

How the study worked

Infraorbital nerve constriction model in male and female Wistar-Hannover rats. Mechanical allodynia measured after CBD or carbamazepine treatment. Brain regions analyzed for Fos-B protein, superoxide oxidation (reactive oxygen species), and glial cell markers (Iba1 for microglia, GFAP for astrocytes).

What this study cannot tell us

Rat model — trigeminal neuralgia in humans may respond differently. Specific doses and routes not detailed in the abstract. Acute treatment effects — long-term efficacy unknown. Mechanistic findings are region-specific and may not capture the full picture.

How to read the evidence

Well-designed preclinical study examining sex differences with multiple mechanistic endpoints, but animal model results need human validation.

When this study was published

Published 2025.

The bigger picture

Sex differences in pain treatment efficacy are increasingly recognized as clinically important. CBD's consistent performance across sexes, combined with its favorable side effect profile compared to carbamazepine, suggests it could address an unmet need in trigeminal neuralgia treatment.

Questions still open

Would CBD be effective for human trigeminal neuralgia patients who don't respond to carbamazepine? Why does CBD show sex-dependent effects in the vlPAG but not the Sp5c? Could CBD be used alongside carbamazepine to enhance efficacy?

Common questions

Could CBD replace carbamazepine for facial nerve pain?

In this rat study, CBD was more consistently effective across sexes and didn't impair movement. However, human clinical trials are needed before CBD could be recommended as a trigeminal neuralgia treatment.

Why do sex differences matter in pain treatment?

Trigeminal neuralgia is more common in women, and many pain medications work differently in men vs. women. CBD's consistent efficacy across sexes is clinically important because it suggests more predictable outcomes regardless of patient sex.

Read the original research

Sex-related differences in cannabidiol's antinociceptive efficacy in a trigeminal neuralgia rodent model.

Pain, 166(10), e336-e350

View on PubMed ↗Publisher’s paper ↗

Citation

Vivanco-Estela, Airam; Rocha, Sanderson Araujo da; Escobar-Espinal, Daniela; Bálico, Gabriela Gonçalves; Caudle, Robert M; Guimaraes, Francisco S; Del-Bel, Elaine; Nascimento, Glauce Crivelaro. (2025). Sex-related differences in cannabidiol's antinociceptive efficacy in a trigeminal neuralgia rodent model.. Pain, 166(10), e336-e350. https://doi.org/10.1097/j.pain.0000000000003616