Medical Research News

Pain-fighting Terpenes

Written by Loren DeVito, PhD

A spotlight on β-caryophyllene

Terpenes pack quite a punch. That first inhale of a new batch of cannabis is full of complex aromas brought to you by the specific terpene profile of that cultivar. While not all appreciate the pungency of cannabis, many connoisseurs greatly enjoy the bouquet of scents offered by the plant as part of its overall sensory experience.

But other than their floral contributions, how much do we really know about terpenes and how else they can enrich cannabis consumption?

Most people are familiar with or have at least heard of the elusive “entourage effect,” which posits that the most comprehensive effects of cannabis can be achieved when its phytochemical components are consumed together. [1] While the modern cannabis industry has migrated into the cannabinoid distillate and isolate space due to interest and demand, there’s abundant potential held within just one bud of flower — and so much that we still don’t know.

A quick literature search will leave you overwhelmed with studies of the “big two” cannabinoids — delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) — and much to be desired regarding minor cannabinoids. What we do know about select terpenes is quite fascinating, considering that their individual contributions have gone unnoticed for so long.

Let’s consider β-caryophyllene. As terpenes are shared among the plant world and not specific to cannabis alone, we’ve all had experiences with terpenes before cannabis came into our lives. β-caryophyllene is also found in black pepper and cloves and imparts a woody aroma. [2] It may even show up on a cannabis product label purchased at a dispensary (depending of course on where you live and what products you buy).

Pre-clinical research has demonstrated that this terpene may hold analgesic properties, which is quite promising considering that many patients use medical cannabis for pain. Of course, pre-clinical data are preliminary and effects must be evaluated in clinical trials — but, many of these findings are quite promising. And the mechanism underlying them is just as intriguing.

A study published a few years ago looked at the role β-caryophyllene in pain perception. [3] The compound capsaicin, which is also found in spicy foods, was used to induce pain in a pre-clinical model. In addition to treatment with β-caryophyllene, cannabinoid 2 (CB2) and opioid receptor antagonists (compounds that block the effects of these systems) were also administered to evaluate their contributions to pain relief.

Researchers found that β-caryophyllene did indeed reduce pain perception — but only when cannabinoid receptors were fully functional. These results indicate that
β-caryophyllene reduces pain by activating the CB2 receptor. Activation appears to also trigger the release of β-endorphin that interacts with certain opioid receptors. [3]

More recent studies have indicated that β-caryophyllene may also be effective in reducing neuropathic pain, which is associated with conditions like chronic hyperglycemia and diabetes. [4,5] Furthermore, data have demonstrated that this analgesic effect is dependent specifically on activation of CB2, but not CB1, receptors. [2,3]

While these findings are preliminary, additional data may suggest that
β-caryophyllene, by itself or in enhanced levels within full-spectrum cannabis, could provide an alternative pain reliever not associated with the intoxication of THC. Stay tuned for updates, as the interest and excitement about terpenes is expected to keep growing.



  1. Russo, E.B. “Taming THC: Potential Cannabis Synergy and Phytocannabinoid-terpenoid Entourage Effects.” Br J Pharmacol, vol.163, no.7, 2011, pp. 1344-1364. (impact factor: 6.81; cited by: 450)
  2. Fidyt, K., et al. “β-caryophyllene and β-caryophyllene Oxide-natural Compounds of Anticancer and Analgesic Properties.” Cancer Med, vol.5, no.10, 2016, pp. 3007-3017. (impact factor: 3.362; cited by: 69)
  3. Katsuyama, S., et al. “Involvement of Peripheral Cannabinoid and Opioid Receptors in β-caryophyllene-induced Antinociception.” Eur J Pain, vol.17, no.5, 2013, pp. 664-675. (impact factor: 3.188; cited by: 55)
  4. Aguilar-Ávila, D.S., et al. “β-Caryophyllene, A Natural Sesquiterpene, Attenuates Neuropathic Pain and Depressive-Like Behavior in Experimental Diabetic Mice.” J Med Food, vol.22, no.5, 2019, pp. 460-468. (impact factor: 1.955; cited by: NA)
  5. Klauke, A.L., et al. “The Cannabinoid CB₂ Receptor-selective Phytocannabinoid β-caryophyllene Exerts Analgesic Effects in Mouse Models of Inflammatory and Neuropathic Pain.” Eur Neuropsychopharmacol, vol.24, no.4, 2014, pp. 608-620. (impact factor: 4.369; cited by: 84)

About the author

Loren DeVito, PhD

Loren DeVito, PhD is a neuroscientist and science writer with expertise in cannabis science and medicine. She is committed to communicating evidence-based information about cannabis and its healing properties. Learn more about her work at

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