Research carried out by scientists from the University of Arizona Health Sciences has shown that cannabis terpenes, compounds found within the plant that produce aroma and taste, could help people combat post-operative and fibromyalgia-linked chronic pain.
The study, published in Pharmacological Reports, is important because the results mean that patients in the future could be offered cannabis-based medicines that reduce pain without the psychoactive ‘stoned’ effects associated with other cannabis compounds, such as tetrahydrocannabinol (THC).
Researchers used a mouse model to investigate how terpenes interact with the A2aR receptor, a major regulator of inflammation.
The study examined four terpenes commonly found in the Cannabis sativa plant: geraniol, linalool, β-caryophyllene and α-humulene. In mouse models of fibromyalgia and post-operative pain, all four compounds produced substantial pain-relieving effects, with geraniol delivering the strongest results.
“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 John Streicher, a professor in the University of Arizona College of Medicine’s Department of Pharmacology and member of the Comprehensive Center for Pain & Addiction.
Fibromyalgia patients and patients who have undergone surgery often experience a tingling sensation, numbness, or pain, known as peripheral neuropathy. Peripheral neuropathy happens when nerves outside of the brain die or become damaged, resulting in disrupted signalling between the brain and the rest of the body.
Previous research has highlighted how cannabis can be a safe and effective medicine for patients living with fibromyalgia, and is particularly helpful for sleep, anxiety, quality of life, and depression.
“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.”
Cannabis has been proven to be effective at combating pain caused by many different conditions. It has also been associated with a reduction in opioid use in people who live with chronic pain.
However, many patients do not want or do not like the ‘high’ effects that come with THC found in most cannabis-based medicines. For instance, patients may feel that they are not able to drive safely, or become too sleepy to function properly after taking a THC-based medicine.
It is for these reasons that researchers investigated the safety and efficacy of non-psychoactive terpenes for the treatment of chronic pain. The terpenes researched in the study were geraniol, linalool, β-caryophyllene, and α-humulene.
The study involved mice that were either put through a paw incision operation or had fibromyalgia induced medically. After researchers established that the mice were in pain, they were administered 200 mg/kg of one of the terpenes via intraperitoneal (IP) injection.
Researchers were able to identify that the terpenes worked by antagonising the A2aR receptor by administering istradefylline.
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 typically temporary, surgery triggers biological changes, including inflammation and increased sensitivity within the body’s pain pathways.
“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.
The team found that 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, which researchers say warrants further investigation.
“These results demonstrate that the terpenes geraniol, linalool, β-caryophyllene, and α-humulene may be a viable medication for post-operative and fibromyalgia pain relief. Their mechanism of action via the A2aR furthers our knowledge of its importance in pain processing and as a target of terpene drugs,” the authors concluded.
