Terpenes for Pain

Written by Tamir Bresler

The entire medical establishment stands poised to accept cannabis and its active constituents as legitimate medicinal compounds. A recent article in the Journal of the American Association of Orthopedic Surgeons advocated for increasing the scrutiny of cannabinoids as a potential alternative to narcotics and anti-inflammatory steroids in the modulation of pain. [1] So besides the attention that’s been given to THC, CBD, and the other cannabinoids in the media, we would like to highlight what’s happening right now in the realm of discovery of terpenes used specifically in the context of pain relief.

Of the terpenes, beta-caryophyllene has shown potential in recent years as a modulator of pain and inflammation. There are two main cannabinoid receptors in the human body, so-called CB1 and CB2, beta-caryophyllene has been shown to selectively activate the CB2 receptor. [2] While CB1 is especially localized in the central nervous system (CNS), CB2 can be found mainly in the peripheries, especially in white blood cells that mediate inflammation and cellular immunity. [3] It’s hypothesized that by beta-caryophyllene binding to and activating the CB2 receptor, it mediates and enhances the same activity as that caused by the cannabinoid class of compounds, providing some scientific rationale for the often bespoken entourage effect.

To that effect, a European study was conducted to see how beta-caryophyllene modulates the pain-relieving capabilities of both strong opioids and molecular mimics of THC termed CB2-agonists. [4] It successfully demonstrated (in mice) that beta-caryophyllene does indeed work through the CB2 receptor, and that it even enhances the pain-relief provided by morphine. The authors postulated that this may illuminate the path towards making a combinatorial beta-caryophyllene and narcotic pharmaceutical mixture to administer for relief of cancer-induced pain. Besides the anti-nociception activity described above, beta-caryophyllene specifically alters several key pathways important for cancer development. [5] Therefore, a pharmaceutical mixture that not only provides pain-relief, but also actively downregulates the cancer from developing itself, obviously represents a win-win situation.

Figure 1. An astrocyte grown in tissue culture stained with Glial Fibrillary Acid Protein (GFAP) and Vimentin.

Switching gears to a discussion of a different terpene and system, another study aimed at testing molecular targets of brain cells that have become actively inflamed. [6] The brain contains two main types cells: neurons, or excitatory cells, and glial, or non-excitatory cells. The purpose of the glial cells is, generally speaking, to support the neurons. Astrocytes (Figure 1 above) are a type of glial cell that carry out a lot of the metabolic activity required to 1) feed neurons, and 2) keep the local electrolyte environment of the neuron well-adjusted. When the CNS undergoes injury, a healing process called gliosis, meaning inflammation of the surrounding glial cells, takes place. The study, which was done in cells in a lab rather than a living being (in vitro), examined the effects of how linalool affects the ability of astrocytes to become less inflamed, and the results showed promise.

There is a large and growing body of research that is exploring the use of terpenes for treating all kinds of pain, from neuropathic and muscular all the way to headaches and migraines. [7] We think that terpene formulations providing tangible relief for pain are going to hit the market hard, and soon.


  1. Krosh, Jeremy, et al. “Cannabinoids Can Serve as Alternatives to Narcotic Pain Medication for Fracture Healing”. AAOS Now. Accessed May 7, 2019.
  2. Gertsch, J. et al. “Beta-caryophyllene is a dietary cannabinoid”. PNAS. 2008; 105(26): 9099-9104 [Times cited = 467, Journal impact factor = 9.504].
  3. Munro, S. et al. “Molecular characterization of a peripheral receptor for cannabinoids”. Nature. 1993; 365(6441): 61-5 [Times cited = 4,470, Journal impact factor = 41.577].
  4. Katsuyama, S. et al. “Involvement of peripheral cannabinoid and opioid receptors in β-caryophyllene-induced antinociception”. Eur J Pain. 2013; 17(5): 664-75 [Times cited = 66, Journal impact factor = 3.218].
  5. Klaudyna, F. et al. “β‐caryophyllene and β‐caryophyllene oxide—natural compounds of anticancer and analgesic properties”. Cancer Med. 2016; 5(10): 3007–3017 [Times cited = 64, Journal impact factor = 3.362].
  6. Hansson, E. et al. “Therapeutic innovation: Inflammatory-reactive astrocytes as targets of inflammation”. IBRO Rep. 2016; 1: 1–9 [Times cited = 4, Journal impact factor = N/A].
  7. Baron, Eric P. “Medicinal Properties of Cannabinoids, Terpenes, and Flavonoids in Cannabis, and Benefits in Migraine, Headache, and Pain: An Update on Current Evidence and Cannabis Science”. Headache. 2018; 58(7): 1139-1186 [Times cited = 6, Journal impact factor = 3.189].

Image Citation: Royal Queen Seeds

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Tamir Bresler

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