The CBD formulation soothed overactive pain receptors without causing memory loss. (© Elroi - stock.adobe.com)

In A Nutshell

• Scientists created a nano-formulation of CBD that reached mouse brains in 30 minutes and restored normal pain thresholds in animals with nerve injury
• The formulation combined cyclodextrin and polysorbate 80 to dramatically boost brain delivery compared to oil-based CBD products
• Treated mice showed no memory problems or motor issues, unlike standard nerve pain medications such as gabapentin
• Brain imaging revealed CBD selectively calmed overactive pain circuits without affecting normal brain function or healthy tissue

A nano-formulation of cannabidiol (CBD) has accomplished something countless pain specialists struggled to achieve. The formulation restores normal pain-response thresholds in mice with chronic nerve injury within 30 minutes, without measurable memory or motor issues in mouse tests.

Scientists at the University of Rochester Medical Center and Boston Children’s Hospital created a delivery system that unlocks CBD’s pain-relieving potential. Published in Cell Chemical Biology, the work points to a new approach that could inform future treatments if human studies bear out the results.

The research team tested their formulation on mice with established nerve injury, which mimics chronic neuropathic pain in humans. Animals treated with a single dose showed normal pain responses within half an hour, and the effect lasted across the test window.

Gabapentin, a first-line nerve pain medication, causes memory problems and dizziness. Opioids carry addiction risks. Meanwhile, pure CBD oil has repeatedly failed in human pain trials, leading many doctors to dismiss the compound.

The problem wasn’t CBD itself but how it was delivered. Oil-based formulations used in clinical trials barely reach the brain. CBD’s waxy nature makes it poorly absorbed, and what enters the bloodstream gets rapidly cleared by the liver.

How the CBD Nano-Formulation Provides Pain Relief

The Rochester-Harvard team combined two pharmaceutical techniques. They trapped CBD molecules inside cyclodextrin rings (inclusion complexes that help keep the drug dissolved), then packaged these complexes into nano-sized bubbles made from polysorbate 80, a common food additive.

This approach substantially raised brain CBD levels compared to standard preparations. Brain concentrations peaked at about 30 minutes, matching the timing of pain relief.

The formulation didn’t numb sensation across the board. Mice treated with CBD-IN maintained normal responses to gentle touch and could still feel heat. They performed normally on memory tests and showed no signs of sedation or motor impairment.

CBD tends to calm dysfunctional brain circuits, yet leaves healthy neural activity alone. (Credit: Fluff Media on Shutterstock

Brain imaging studies showed CBD specifically quieted hyperactive pain circuits in the spinal cord, thalamus, and sensory cortex. Brain regions unrelated to pain showed no changes in activity. Gabapentin, by contrast, broadly dampened all sensory responses and impaired performance on cognitive tasks.

In isolated spinal cord tissue, researchers watched individual nerve cells respond to a chemical that mimics the hyperexcitable state seen in chronic pain. Applying CBD at concentrations matching those in living animals rapidly suppressed this abnormal firing.

Live brain imaging in freely moving mice revealed something more interesting. In healthy animals, CBD didn’t affect how sensory cortex neurons responded to touch. But in animals with nerve injury, where these same neurons had become pathologically overactive, CBD restored normal response levels. CBD preferentially targets dysfunctional circuits while leaving healthy neural activity intact.

Path to Human Use

Both components are commonly used, FDA-listed excipients, though the formulation itself has not been tested in people yet. Polysorbate 80 appears in numerous medications and foods. Cyclodextrin enhances drug delivery in several approved products.

The team tested oral administration as well. A 50-milligram oral dose produced similar rapid relief, with CBD reaching the brain faster than the sesame oil formulation used in Epidiolex, the only FDA-approved CBD medication. CBD showed relatively rapid hepatic clearance, which could ease liver-related concerns, something to test in people.

What the Research Doesn’t Answer

This research used mice with surgically induced nerve damage, a well-established model for neuropathic pain. Still, it is not identical to human conditions. The study tracked effects for several hours after a single dose. Questions remain about long-term dosing in people. In mice, five doses given on alternate days kept working without signs of tolerance.

The nano-formulation hasn’t been tested in humans. Safety studies and clinical trials would be needed before this could reach patients. Researchers couldn’t identify exactly which molecular targets CBD acts on, though they ruled out the main cannabinoid receptors.

These results, while promising, stem from a well-established mouse model of neuropathic pain. The formulation’s human efficacy and dosing remain open questions.

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Disclaimer: This research was conducted in mice with surgically induced nerve damage. The formulation has not been tested in humans, and safety and efficacy in people remain unknown.

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Paper Summary

Methodology

Researchers created a nano-micelle formulation of CBD by forming inclusion complexes with hydroxypropyl-β-cyclodextrin, then encapsulating these in polysorbate 80 nano-micelles. They characterized the formulation using cryogenic transmission electron microscopy and mass spectrometry. The team induced neuropathic pain in mice through spared nerve injury surgery, then tested various doses of CBD-IN administered intraperitoneally or orally. Behavioral testing assessed mechanical sensitivity using von Frey filaments, alongside cognitive and motor function tests. Neural activity mapping used activity-dependent genetic reporters in spinal cord and brain tissue. Live calcium imaging tracked sensory cortex neurons in freely moving animals. Ex vivo experiments examined CBD effects on spinal cord tissue in isolation.

Results

CBD-IN achieved significantly higher brain concentrations than conventional formulations, reaching peak levels at 30 minutes. A 100 mg/kg intraperitoneal dose completely restored normal pain thresholds in mice with established neuropathic pain. The formulation reduced both mechanical allodynia and cold sensitivity without affecting normal sensory responses or heat pain perception. Treated mice performed normally on cognitive tests, motor coordination tasks, and showed no signs of sedation. Neural mapping revealed reduced activation in pain-processing regions including spinal dorsal horn laminae I-II, ventrobasal thalamus, primary somatosensory cortex, and insular cortex. CBD specifically suppressed hyperactive responses in diseased circuits while preserving normal neural activity in healthy tissue and brain regions unrelated to pain processing.

Limitations

The study used male and female mice between 8-16 weeks old, which may not fully represent older populations where chronic pain is more prevalent. The spared nerve injury model mimics neuropathic pain but doesn’t capture all aspects of human chronic pain conditions. Researchers measured effects over hours following single doses, leaving questions about long-term efficacy, optimal repeated dosing schedules, and potential tolerance development. The precise molecular targets mediating CBD’s effects remain incompletely defined, though CB1 and CB2 receptors were ruled out through antagonist studies. Some CBD was lost to binding with plastic containers during formulation, reducing actual delivered doses to about 43% of intended amounts. Human bioavailability, safety profiles, and clinical efficacy remain unknown and would require dedicated trials.

Funding and Disclosures

Funding: NIH grant R01AT010779. The University of Rochester has filed US Provisional Patent application (no. 63/662,516) and an International Patent Application (no. PCT/US25/34093) for the CBD nano-formulation technology, with several authors listed as co-inventors. The researchers reported no other competing financial interests.

Publication Details

Feng J, Page J, Chung L, He Z, Wang KH. “Rapid suppression of neuropathic pain and somatosensory hyperactivity by nano-formulated cannabidiol,” published in Cell Chemical Biology. 2025;32:1-17, November 20, 2025. doi:10.1016/j.chembiol.2025.10.005

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