Scientists Just Found a THC-Free Cannabis Compound That May Replace Opioids

Terpenes from cannabis may relieve chronic pain without THC’s psychoactive effects.

Researchers found that certain terpenes significantly reduced fibromyalgia and post-surgical pain in animal studies, with geraniol showing the most promise.

Terpenes: A Potential Breakthrough for Pain Relief

Terpenes from the Cannabis sativa plant may offer a promising new approach to treating fibromyalgia and post-surgical pain, according to research from the University of Arizona Health Sciences, published in Pharmacological Reports.

This study builds on earlier research led by Dr. John Streicher, a member of the Comprehensive Center for Pain & Addiction, which demonstrated the pain-relieving effects of terpenes in models of inflammation and chemotherapy-induced neuropathic pain.

Targeting Chronic Pain Over Acute Pain

“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.”

Terpenes, the natural compounds responsible for plants’ distinct aromas and flavors, provide a potential alternative for pain relief without the psychoactive effects of tetrahydrocannabinol (THC).

Testing Terpenes: The Four Key Players

Streicher and the research team tested four terpenes found in moderate to high levels in Cannabis sativa: geraniol, linalool, beta-caryophyllene, and alpha-humulene.

They found that each of the terpenes resulted in high levels of pain relief in mouse models of post-operative pain and fibromyalgia. Geraniol provided the most significant level of pain relief, followed by linalool, beta-caryophyllene, and alpha-humulene.

A Promising New Approach for Fibromyalgia

“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.”

Fibromyalgia is a chronic musculoskeletal disorder that affects up to 5% of the world’s population, according to research published in Healthcare (Basel) in 2023. The U.S. Department of Health and Human Services’ Office on Women’s Health estimates about 4 million U.S. adults have fibromyalgia, which affects women more than men.

Post-surgical pain straddles the line between acute pain and chronic pain. It is usually short in duration, but it also involves physiological changes such as increased inflammation and sensitization of the body’s pain system that contribute to the pain.

Beyond Opioids: A Safer Alternative?

“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.”

Globally, approximately 310 million major surgeries are performed each year, according to 2020 research published in the International Journal of Surgery.

Nature’s Hidden Medicines

“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,” said 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.

“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 Terpenes Work: A Caffeine Connection?

The study also demonstrated that the mechanism of action of terpenes on post-surgical and fibromyalgia pain was the same as in previous studies. Its action through the adenosine A_2a receptor, a receptor that caffeine targets and blocks, suggests a sedative effect that could be the subject of future research.

Reference: “Select terpenes from Cannabis sativa are antinociceptive in mouse models of post-operative pain and fibromyalgia via adenosine A2a receptors” by Caleb A. Seekins, Alyssa M. Welborn, Abigail M. Schwarz and John M. Streicher, 12 December 2024, Pharmacological Reports.
DOI: 10.1007/s43440-024-00687-1

Streicher’s co-authors were Caleb Seekins, who worked in Streicher’s lab as an undergraduate biochemistry student and is now pursuing a medical degree at the College of Medicine – Tucson; Alyssa Welborn, who graduated with a Bachelor of Science in Pharmaceutical Sciences in 2024; and Abigail Schwarz, who finished her doctorate in Streicher’s lab in 2024.

This study was funded by the National Institutes of Health under award no. R01AT011517.

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