Nano-encapsulated CBD offers potential pain relief with no adverse side effects

Reaching for CBD-infused lotion or oil may seem like a low-risk way to find pain relief, but little is actually known about the impact that CBD has on the nervous system.

Over the past decade, the use of cannabis products for pain management has increased, in part because in 2018, Congress signed a law removing hemp from the federal Controlled Substances Act, thereby legalizing hemp-derived CBD. Today, it is most commonly found in oil form, as well as in lotions and cosmetics, and it is widely understood that CBD does not cause a “high.”

However, what CBD does in the human body and brain is not well understood. Currently, the Food and Drug Administration has only approved CBD as an adjunctive treatment for certain forms of epilepsy, and it is not recommended for use during pregnancy.

“We need to understand more about this compound, what mechanisms it interacts with in the brain, its impact on the body, and whether it is a potentially safer solution for treating the chronic pain epidemic,” said Kuan Hong Wang, Ph.D., professor of Neuroscience and member of the Del Monte Institute for Neuroscience at the University of Rochester, whose lab in collaboration with researchers at Harvard Medical School and Boston Children’s Hospital, recently discovered that in mice, they could effectively deliver CBD to the brain for neuropathic pain relief with no adverse side effects.

This research was published in the journal Cell Chemical Biology.

Devising a delivery method

The first hurdle researchers had to cross was the blood-brain barrier. This part of our anatomy does an incredible job of keeping our brain healthy, as it essentially acts as a protective force field around the brain. Because of this barrier and the fact that CBD does not dissolve well in water, very little CBD reaches the brain when taken in its common oil form.

Staff scientist Jingyu Feng, Ph.D., in the Wang Lab, and the first author of the study, helped develop the delivery mechanism: inclusion-complex-enhanced nano-micelle formulation or CBD-IN. CBD-IN is a method that encapsulates CBD molecules within nano-micelles or water-soluble spheres that are considered safe in food and drugs.

Researchers found that when CBD-IN was given to mice, it provided pain relief within 30 minutes, and with none of the common adverse side effects, like loss of movement, balance, or memory, that often occur when taking conventional pain drugs.

“The pain relief also lasted through repeated use,” said Feng. “We did not see its effect wear off over time.”

Impact on the brain

Using imaging and genetic mapping tools, researchers revealed that when CBD-IN is ingested by mice, it calms overactive nerve circuits in the areas of the brain and spinal cord responsible for sensing touch and pain. This calming effect only occurs where abnormal activation is present, like after a nerve injury. Importantly, CBD-IN does not affect healthy neurons.

Researchers were surprised to discover that the pain-relieving effect did not rely on the typical cannabinoid receptors (CB1 and CB2) that THC and other cannabis compounds target in the body.

“Instead, CBD-IN seems to influence broader electrical and calcium signaling in nerve cells, offering a new way to control nerve hyperactivity without triggering the ‘high’ or dependency risks associated with traditional cannabinoids or opioids,” Feng said.

“The broader implication of this research is that nanotechnology can make natural compounds like CBD more effective and precise,” said Wang, co-senior author of this research.

“By enhancing brain delivery and targeting only disease-related neural overactivity, this strategy could open new doors for treating chronic pain and possibly other neurological disorders, such as epilepsy or neurodegenerative diseases, where abnormal nerve activity plays a central role.”