Scientists Finally Figure Out How to Get CBD to the Brain for Pain Relief

Using CBD-infused oils or lotions might seem like a simple, low-risk way to ease pain, yet scientists still have much to learn about how CBD affects the nervous system.

In the past ten years, cannabis-based products have become increasingly popular for managing pain. This trend grew after Congress passed a 2018 law that removed hemp from the federal Controlled Substances Act, making hemp-derived CBD legal. Today, CBD is widely available in oils, creams, and cosmetics, and it is commonly recognized that it does not produce a ‘high’.

Despite its popularity, researchers still do not fully understand how CBD interacts with the body and brain. At present, the Food and Drug Administration has approved CBD only as an additional treatment for certain types of epilepsy, and it advises against its 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, PhD, 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.

Devising a Delivery Method

One of the main challenges researchers faced was finding a way for CBD to pass through the blood-brain barrier. This structure serves as the brain’s natural defense system, filtering out potentially harmful substances to keep it healthy. Because this barrier blocks most compounds and CBD does not dissolve easily in water, only a small amount can reach the brain when consumed in its typical oil form.

To overcome this problem, staff scientist Jingyu Feng, PhD, of the Wang Lab and lead author of the study, helped create a new delivery method known as inclusion-complex-enhanced nano-micelle formulation (CBD-IN). This approach encloses CBD molecules inside tiny, water-soluble spheres called nano-micelles, which are approved as safe for use in foods and pharmaceuticals.

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.”

By University of Rochester Medical Center