Besides cannabinoids, terpenes are among the most important and well-known compounds in hemp. They are responsible not only for the individual aroma of each strain but also create a synergistic effect with cannabinoids and other plant compounds. However, isolated terpenes are also pharmacologically active. The potential benefits of terpenes in pain medicine should not be underestimated. While terpenes cannot relieve acute pain, they are a major source of hope in treating chronic pain. Given the prevalence of chronic pain and the often severe side effects of conventional painkillers, further research in this area is urgently needed. In 2025, several new studies were published showing great promise for terpenes‘ potential.
📑 Inhaltsverzeichnis
- Effective through a relatively unknown receptor
- Potentially effective for postoperative and neuropathic pain
- Pain relief through an anti-inflammatory mechanism of action
- Potentially helpful in tapering off opioids
- Favorable side effect profile
- Frequently asked questions about terpenes in pain medicine
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Effective through a relatively unknown receptor
One receptor that has barely appeared in connection with hemp until now is the adenosine A2a receptor. According to current scientific findings, a substantial portion of the pain-relieving effect of some terpenes appears to be mediated through this receptor. The receptor was named after the body’s own substance adenosine, which binds to this receptor. Adenosine is a component of the energy carrier adenosine triphosphate, which performs life-sustaining functions in the body. The mentioned receptor is found in many types of cells and performs numerous functions that have not yet been fully researched. Among other things, it regulates oxygen demand in the heart and participates in numerous immunological processes. Like the well-known cannabinoid receptors, the adenosine A2a receptor also belongs to the G-protein-coupled receptor family. This means that the corresponding substance docks at a protein on this receptor and then triggers certain signals and processes inside the cell. Terpenes from hemp apparently play a role in fighting pain through this receptor. Research on the adenosine A2a receptor expands our understanding of the development of chronic pain and possible new treatment methods.
Potentially effective for postoperative and neuropathic pain
A 2025 US study was able to find evidence through observations in mice that certain terpenes can relieve neuropathic and postoperative pain through the mentioned receptor. The effect lasted three hours and could be reversed using the A2a antagonist istradefylline. This allowed researchers to conclude that the observed effect was indeed caused by terpenes acting on this receptor. Several terpenes were tested for this property. This effect was most pronounced with geraniol, linalool, β-caryophyllene, and α-humulene. The same mechanism of action was independently confirmed in another study.
This 2025 published study also examined the effects of terpenes through observations in mice. Researchers found that terpenes like geraniol and linalool can relieve neuropathic pain through the adenosine A2a receptor. In this study too, a control test was performed with the adenosine A2a antagonist istradefylline, which reversed this effect. Particularly effective in these observations were the inhibitions of pain signaling pathways typically associated with postoperative or neuropathic pain. Although clinical trials are still pending, future postoperative use in humans is conceivable to enhance the effects of existing medications or, through dose reduction, minimize side effects.
Pain relief through an anti-inflammatory mechanism of action
A research paper published in 2025 from Italy summarized numerous properties of terpenes previously known from preclinical studies that make them a valuable tool in fighting pain. Some terpenes work through TRPV receptors. The TRPV1 receptor in particular has repeatedly come into focus in recent years as a possible therapeutic target for pain management. Many terpenes also have anti-inflammatory properties. Since many types of chronic pain arise from or are at least promoted by inflammatory processes, terpenes are also a possible treatment option here.
Arthritis and other rheumatic diseases in particular are widespread conditions that are accompanied by chronic pain. Some terpenes show a regulatory effect on a messenger substance called NF-Kappa-B. This is a protein found in virtually all cells that has a modulatory effect on inflammatory processes. Dysregulation of NF-Kappa-B is associated with numerous inflammations that can, among other things, lead to chronic pain. An inhibitory effect on NF-Kappa-B has been demonstrated particularly with pinene. Furthermore, it is known that numerous terpenes also interact with the enzyme cyclooxygenase-2. This enzyme is also significantly involved in inflammation, so regulating its activity can indirectly be useful in chronic pain.
Among other things, the cannabinoids CBD and CBG also have an inhibitory effect on cyclooxygenase-2, which explains part of their anti-inflammatory effect. Cyclooxygenase-2, or COX-2, is also the therapeutic target of many nonsteroidal antirheumatic drugs such as diclofenac. The same effect has been demonstrated with some terpenes. Particularly interesting in this context is beta-caryophyllene. This special terpene, which also acts on the CB2 receptor and thus is also a cannabinoid, can also contribute to pain relief. Studies have shown that beta-caryophyllene releases the body’s own opioids, called beta-endorphins, which contributes to its pain-relieving effects.
Potentially helpful in tapering off opioids
There is preclinical evidence that terpenes could be helpful in tapering off opioids. Opioids are often standard medication in pain therapy and are indispensable for acute pain, but in the treatment of chronic pain they bring a series of serious problems such as dependence. As mentioned, beta-caryophyllene indirectly stimulates the release of the body’s own opioid beta-endorphin. A recently published study provided evidence that this effect could be useful when discontinuing opioids. Through observations in rats, it was shown that self-administration of opioids decreases significantly when beta-caryophyllene is administered. These observations suggest that this terpene could offer support to pain patients in discontinuing opioids after long-term use.
Favorable side effect profile
Most terpenes from hemp are largely safe, which is why they have long been approved as additives in food and cosmetics. For example, limonene, which has been studied in many studies, shows no or only very mild side effects such as gastrointestinal complaints even at an oral dose of eight grams per day. However, a possible allergic reaction at high concentrations with topical application must not be overlooked.
Many terpenes can cause skin irritation here. Drug interactions, particularly with those metabolized in the liver via CYP enzymes, have not yet been fully clarified. In vitro studies have shown that limonene and pinene inhibit certain activities of the liver enzyme CYP-450. This enzyme plays a central role in the metabolism of many drugs. Further research and especially clinical trials are needed to fully clarify these questions. Nevertheless, it can be said that terpenes are comparatively non-toxic, unlike opioids they have no addiction potential, and they will gain even greater importance in the future in the treatment of chronic pain.
Frequently asked questions about terpenes in pain medicine
Which terpenes work best against chronic pain?
In current studies, geraniol, linalool, β-caryophyllene, and α-humulene showed the strongest pain-relieving effects – mediated through the adenosine A2a receptor. Our guide to the 20 most important cannabis terpenes and their effects provides an overview of all relevant profiles. How well cannabis overall helps with chronic pain is summarized in our article on the effectiveness of cannabis against chronic pain.
How does beta-caryophyllene relieve pain?
As one of the few terpenes, beta-caryophyllene directly activates the CB2 receptor and also stimulates the release of the body’s own beta-endorphins. More on this dual nature of terpene and cannabinoid is explained in our article Beta-caryophyllene – the special terpene in hemp.
Can terpenes help reduce opioid use?
Preclinical studies suggest that beta-caryophyllene may reduce self-administration of opioids and could support tapering. Its potential is also being investigated in adjunctive therapy for cancer patients – more on this in our analysis of pain relief through terpenes in chemotherapy.
Do terpenes also help with osteoarthritis and inflammatory pain?
Many terpenes have anti-inflammatory effects, for example through NF-Kappa-B and the enzyme COX-2, which is also inhibited by antirheumatic drugs. Myrcene in particular is coming into focus – details are provided in our article on the effects of myrcene on pain and osteoarthritis.
Sources
2 Adenosine A2a studies:
https://pubmed.ncbi.nlm.nih.gov/39663308/
https://www.sciencedirect.com/science/article/abs/pii/S030439402500093X
Italian study
https://pubmed.ncbi.nlm.nih.gov/40872493/
https://www.mdpi.com/1424-8247/18/8/1100
NF-Kappa-B and cyclooxygenase-2 explained:
https://de.wikipedia.org/wiki/NF-%CE%BAB
https://de.wikipedia.org/wiki/Cyclooxygenase-2
Section 3.4, side effect profile of terpenes:
https://pmc.ncbi.nlm.nih.gov/articles/PMC12389225/
Opioid tapering study:
Hast du schon einmal Terpene gezielt zur Schmerzlinderung verwendet?
https://pubmed.ncbi.nlm.nih.gov/38631564/
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