The study builds on earlier work from the lab of John Streicher, PhD, a member of the Comprehensive Center for Pain & Addiction, which found that terpenes could reduce pain in models of inflammation and chemotherapy-related nerve damage.

"Our research is showing that terpenes are not a good option for reducing acute pain resulting from an injury, such as stubbing your toe or touching a hot stove; however, we are seeing significant reductions in pain when terpenes are used for chronic or pathological pain," said Streicher, who is a professor in the U of A College of Medicine -- Tucson's Department of Pharmacology. "This study was the first to investigate the impact of terpenes in preclinical models of fibromyalgia and post-operative pain and expand the scope of potential pain-relieving treatments using terpenes."

Cannabis Terpenes Show Strong Pain Relief

Terpenes are natural compounds responsible for the scent and flavor of many plants. In cannabis, they contribute to the plant's distinctive aroma and may also have medicinal properties.

Unlike tetrahydrocannabinol, or THC, terpenes do not produce the unwanted psychoactive effects commonly associated with cannabis. That makes them an appealing area of research for scientists searching for new pain treatments.

For this study, researchers examined four terpenes commonly found in Cannabis sativa: geraniol, linalool, beta-caryophyllene, and alpha-humulene.

In mouse models of fibromyalgia and post-operative pain, all four compounds produced substantial pain-relieving effects. Geraniol delivered the strongest results, followed by linalool, beta-caryophyllene, and alpha-humulene.

New Hope for Fibromyalgia Treatment

Fibromyalgia remains one of the most challenging chronic pain conditions to treat. The disorder affects muscles and soft tissues throughout the body and is estimated to impact up to 5% of the global population, according to research published in Healthcare (Basel) in 2023.

In the United States alone, about 4 million adults have fibromyalgia, according to the U.S. Department of Health and Human Services' Office on Women's Health. Women are affected more often than men.

"With fibromyalgia, there isn't much understanding of what the pain state is, and there are not a lot of great options for treating it," Streicher said. "Our findings show that terpenes may be a viable treatment option for fibromyalgia pain, which could potentially have a large impact and make a difference for an under-treated population."

Potential Alternative for Post-Surgical Pain

The researchers also explored whether terpenes could help with pain following surgery.

Post-surgical pain occupies a unique middle ground between acute and chronic pain. Although it is typically temporary, surgery triggers biological changes including inflammation and increased sensitivity within the body's pain pathways, which can intensify discomfort.

"Opioids do a good job controlling post-surgical pain, but they can cause constipation that can increase the chances of post-surgical complications such as adhesions," Streicher said. "We are always looking for better options, and this study suggests that terpenes could be a novel therapeutic for post-operative pain."

According to research published in the International Journal of Surgery in 2020, roughly 310 million major surgical procedures are performed worldwide each year, highlighting the need for safer and more effective pain-management options.

Natural Compounds Continue to Surprise Scientists

Todd Vanderah, PhD, director of the Comprehensive Center for Pain & Addiction at U of A Health Sciences and professor and head of the Department of Pharmacology at the U of A College of Medicine -- Tucson, said the findings underscore the value of exploring chemicals produced by nature.

"The research that is being done by Dr. Streicher's lab on terpenes and their potential to help those who suffer from chronic pain demonstrates the importance of basic research. There are hundreds of unique chemicals that plants make, including the Cannabis plant, that are undiscovered," Vanderah said.

"Nature is incredible at making unique chemical structures, and many of these chemicals are unknowns when it comes to their abilities to aid in human health, diseases and disorders. A great current example is medication semaglutide, sold under the brand name Ozempic, which has a chemical structure that was isolated not from a plant, but from an animal that is prevalent in the Southwest, the Gila monster. These discoveries from natural products through research such as Dr. Streicher's can result in very useful medications."

How the Terpenes May Work

The team also found that the compounds appeared to act through the same biological pathway identified in previous terpene studies.

Specifically, the pain-relieving effects were linked to the adenosine A2a receptor -- a receptor that caffeine targets and blocks -- suggesting that terpenes may also have sedative properties. Researchers say that possibility warrants further investigation.

The study's co-authors included Caleb Seekins, a former undergraduate biochemistry student in Streicher's lab who is now pursuing a medical degree at the College of Medicine -- Tucson; Alyssa Welborn, who earned a Bachelor of Science in Pharmaceutical Sciences in 2024; and Abigail Schwarz, who completed her doctorate in Streicher's lab in 2024.

Funding for the research was provided by the National Institutes of Health under award no. R01AT011517.