Chronic pain, particularly neuropathic pain resulting from nerve damage, significantly impacts quality of life for many individuals. Conventional treatments, such as opioids, often come with severe side effects like addiction, tolerance, and constipation, making them less ideal for long-term management.
Recent research published in the journal PAIN explores an alternative: terpenes from Cannabis sativa. The study found that certain terpenes are as effective as morphine in reducing chronic neuropathic pain. Furthermore, combining terpenes with morphine enhanced pain relief without increasing side effects.
Previous studies have shown that the primary cannabinoids in Cannabis, tetrahydrocannabinol (THC) and cannabidiol (CBD), can manage chronic pain, but their effectiveness is moderate, and THC often causes psychoactive side effects. This led researchers to investigate terpenes, the aromatic compounds in plants, which may offer pain relief without these drawbacks. The study aimed to determine if terpenes could manage chronic pain effectively and safely.
Researchers led by John Streicher of the University of Arizona focused on five terpenes commonly found in Cannabis: alpha-humulene, beta-caryophyllene, beta-pinene, geraniol, and linalool. They used a mouse model of chemotherapy-induced neuropathic pain, which mimics chronic pain conditions in humans.
Mice were treated with paclitaxel, a chemotherapy drug, to induce neuropathic pain. Their pain responses were measured using mechanical sensitivity tests. The mice then received either one of the terpenes, morphine, or a combination of both. Researchers evaluated the pain relief provided by each treatment by observing changes in pain sensitivity over time.
Each of the five terpenes tested provided significant pain relief comparable to morphine. This was a remarkable discovery, suggesting that terpenes alone could be potent pain relievers.
“A question that we’ve been very interested in is could terpenes be used to manage chronic pain?” said Streicher. “What we found is that terpenes are really good at relieving a specific type of chronic pain with side effects that are low and manageable.”
When combined with morphine, terpenes enhanced the pain relief effects without increasing the negative side effects associated with opioids. This combination therapy could allow for lower doses of morphine, reducing the risk of addiction and other side effects.
Terpenes did not show any rewarding or addictive properties in the mice, suggesting a lower risk of addiction. Additionally, terpenes did not produce significant tolerance over time, meaning their effectiveness did not diminish with repeated use, unlike morphine.
“That was really striking to us, but just because something relieves pain doesn’t necessarily mean it’s going to be a good therapy,” Streicher said. “This brings up the idea that you could have a combination therapy, an opioid with a high level of terpene, that could actually make the pain relief better while blocking the addiction potential of opioids. That’s what we are looking at now.”
The researchers identified that the terpenes likely relieve pain by activating the adenosine A2A receptor, particularly in the spinal cord. This receptor plays a role in reducing pain and inflammation, providing a new target for pain management strategies.
While the study presents promising results, there are several limitations and considerations for future research. The study was conducted in mice, and while animal models provide valuable insights, human physiology can respond differently. Clinical trials in humans are necessary to confirm the efficacy and safety of terpenes for pain relief.
The researchers also found that terpenes had limited effectiveness when administered orally or via inhalation, which are more practical for human use. Future research should focus on improving the bioavailability of terpenes through advanced formulation techniques, such as nanoparticle delivery systems.
“A lot of people vape or smoke terpenes as part of cannabis extracts that are available commercially in states where cannabis use is legal,” Streicher said. “We were surprised to find that the inhalation route didn’t have an impact in this study, because there are a lot of at least anecdotal reports saying that you can get the effects of terpenes whether taken orally or inhaled. Part of the confounding factor is that terpenes smell quite nice and it’s hard to disguise that aroma, so people could be kind of having the psychosomatic placebo-style effect.”
The study, “Terpenes from Cannabis sativa induce antinociception in a mouse model of chronic neuropathic pain via activation of adenosine A2A receptors,” was authored by Abigail M. Schwarz, Attila Keresztes, Thai Bui, Ryan J. Hecksel, Adrian Peña, Brianna Lent, Zhan-Guo Gao, Martín Gamez-Rivera, Caleb A. Seekins, Kerry Chou, Taylor L. Appel, Kenneth A. Jacobson, Fahad A. Al-Obeidi, and John M. Streicher.
