Cannabis Sativa Terpenes Show Promise in Improving Post-Operative, Fibromyalgia Pain

New research found that select terpenes from cannabis sativa, namely geraniol, linalool, β-caryophyllene, and α-humulene, may relieve post-operative and fibromyalgia pain.1

The research also elucidated the mechanism of action of the terpenes via the A2aR, which investigators state furthers knowledge of its importance in pain processing and as a target of terpene drugs.

“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,” senior investigator John Streicher, PhD, professor in the University of Arizona College of Medicine – Tucson’s Department of Pharmacology, said in a statement.2 “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.”

Streicher and colleagues measured baseline mechanical sensitivity in male and female CD-1 via von Frey filaments and underwent either paw incision surgery or reserpine-induced fibromyalgia (0.32 mg/kg, sc). After establishing pain in the mice, investigators administered 200 mg/kg ip of a terpene and measured mechanical sensitivity over 3 hours. They gave the mice the A2aR antagonist istradefylline (3.2 mg/kg, ip) 10 min before terpene, with mechanical sensitivity measured after, to determine the potential mechanism of action. They also performed hot plate pain testing as a control.1

The investigators found that, in both pain models, mice receiving terpene treatment had time-dependent elevations of the mechanical thresholds, with the strongest effect with geraniol, then linalool or α-humulene. Streicher and colleagues noted that these findings indicated that the 4 terpenes are anti-nociceptive in post-surgical and fibromyalgia pain. They also found that pretreatment with istradefylline blocked antinociception, suggesting the A2aR mechanism of action for terpenes in these pain models. Furthermore, terpenes had no effect on hot plate latencies, ruling out non-specific motor effects.1

“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,” Todd Vanderah, PhD, director of the Comprehensive Center for Pain & Addiction at the U of A Health Sciences and professor and head of the Department of Pharmacology at the U of A College of Medicine – Tucson, added.2 “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.”

REFERENCES

1. Seekins CA, Welborn AM, Schwarz AM, Streicher JM. Select terpenes from Cannabis sativa are antinociceptive in mouse models of post-operative pain and fibromyalgia via adenosine A2a receptors. Pharmacol Rep. 2025;77(1):172-181. doi:10.1007/s43440-024-00687-1

2. Cannabis terpenes offer potential new way to treat fibromyalgia pain. News release. University of Arizona Health Sciences. March 12, 2025. https://www.eurekalert.org/news-releases/1076744