Chronic pain is a global health challenge, with current treatment options often limited by side effects, addiction risk, and diminished effectiveness over time. In a new study, Yale researchers identify alternative compounds with therapeutic potential — chemicals found in cannabis that lack the mind-altering effects associated with the drug.
The chemicals — cannabidiol (CBD), cannabigerol (CBG), and cannabinol (CBN), which belong to a group of molecules known as cannabinoids — reduced the activity of a protein that is central to pain signaling in the peripheral nervous system, the study showed.
The findings, published Jan. 21 in the Proceedings of the National Academy of Sciences, offer a promising new approach for safe and effective pain relief, said the researchers.
“These findings open new avenues for the development of cannabinoid-based therapies,” said Mohammad-Reza Ghovanloo, lead author of the study and an associate research scientist in the Department of Neurology at Yale School of Medicine. “Our results show that CBG in particular has the strongest potential to provide effective pain relief without the risks associated with traditional treatments.”
Those risks include addiction, which is associated with opioids, one class of drugs prescribed for severe pain. The United States continues to be affected by the opioid epidemic — more than 80,000 people have died annually from opioid overdoses in recent years.
Cannabinoids may also yield more effective pain management than other opioid alternatives, Ghovanloo added.
The cannabinoids highlighted in the study interact with a protein found in the cell membrane of sensory neurons in the spine. The protein, called Nav1.8, enables repetitive firing of those neurons, which is a key process in transmitting pain signals. Blocking Nav1.8, and thereby muting its activity, has shown promise in reducing pain in recent clinical studies.
In the new study, the researchers measured the electrical current in rodent sensory neurons and how the current changed when CBD, CBG, and CBN were introduced. Each of the three cannabinoids reduced the cells’ electrical current amplitudes associated with Nav1.8. Of the three, CBG inhibited Nav1.8 action most strongly.
The findings indicate that these three cannabinoids — and CBG in particular — can prevent sensory neurons in the body from sending pain signals to the brain. The researchers are optimistic that these compounds could provide a safer alternative for pain management and reduce reliance on opioids.
“This research builds on the growing interest in the therapeutic potential of cannabinoids, highlighting their role in addressing chronic pain conditions such as neuropathic pain, arthritis, and inflammatory disorders,” said Dr. Stephen G. Waxman, senior author of the study and the Bridget M. Flaherty Professor of Neurology at Yale School of Medicine. “By focusing on Nav1.8 as a therapeutic target, the study paves the way for the development of innovative, cannabinoid-based pain treatments.”
