This past year has been quite notable for the advancement of cannabis science and research. Several studies have been published in high-impact, peer-reviewed journals, and the first cannabis-based therapeutic was approved by the FDA to treat severe forms of pediatric epilepsy. [1-3] With the proliferation of this research comes a greater understanding of Cannabis sativa, its wide array of bioactive ingredients, and how it may be used to prevent or treat disease.
The majority of research on cannabis has been conducted on the two most familiar compounds – cannabidiol (CBD) and tetrahydrocannabinol (THC). However, the lesser-studied terpene constituents, also produced in the trichomes, have been shown to possess key biochemical properties that make them well-suited for therapeutic applications. [4] Terpenes are also believed to interact with cannabinoids to produce an “entourage effect” – a synergy of biochemical interactions that provide holistic medicinal benefits.
While terpenes are essential components of cannabis, they are by no means exclusive to it, as they can be found in flowering plants. Limonene contributes to the fragrance of citrus. Linalool is a of lavender. The shared chemical properties across terpenes and their physiological effects have provided clues as to the specific medicinal properties of cannabis-derived terpenes.
Pre-clinical trials have shown that certain terpenes possess anti-oxidant properties. [5] While many consumer products are labeled as “antioxidants” to promote health, only substances proven to prevent the oxidation of fundamental biological compounds such as proteins, carbohydrates, and fats, are scientifically considered “antioxidants.”
When oxygen is broken down in the body, it produces free radicals, or atoms with unpaired electrons. An abundance of free radicals can causes damage, as they are highly reactive and unstable – this is called oxidative stress. The damage caused by oxidative stress has been linked to multiple conditions, including autoimmune and cardiovascular diseases. [6] Nitric oxide (NO), an essential signaling molecule in the body, is a free radical, and, during the process of creating NO, additional free radicals are produced. [7] NO levels have been linked to increased oxidative stress and associated disease.
While erroneous (or exaggerated) claims abound, several terpenes, such as those found in rosemary, are proven to possess antioxidant properties through inhibition of NO production. [8] Similar effects have been found for cannabis terpenes. One study evaluated three cannabis chemotypes and analyzed their terpenoid content. Applying high concentrations of different terpenes inhibited production of NO in cell cultures and reduced production of reactive oxygen intermediates, byproducts of oxygen metabolism [9]. These terpenes also reduced swelling and pain perception (measured by muscle retraction) in an animal model of paw inflammation.
Another study found that myrcene significantly reduced NO production in a cellular model of osteoarthritis. [10] However, this effect was exclusive to myrcene; while limonene produced a smaller degree of inhibition, βshowed no effect. These results indicate that some terpenes may possess more potent effects on oxidative stress than others.
Additional research is necessary to better understand how terpenes impact NO production, as well as other forms of oxidative stress, to better evaluate how they could be potentially used as antioxidants.
References
- Pasman, J.A., et al. “GWAS of Lifetime Cannabis Use Reveals New Risk Loci, Genetic Overlap with Psychiatric Traits, and a Causal Influence of Schizophrenia.” Nature Neurosci, vol.21, no.9, 2018, pp. 1161-1170 (impact factor: 19.912; cited by: 16)
- Bhattacharyya, S., et al. “Effect of Cannabidiol on Medial Temporal, Midbrain, and Striatal Dysfunction in People at Clinical High Risk of Psychosis: A Randomized Clinical Trial.” JAMA Psychiatry, vo.75, no.11, 2018, pp. 1107-1117 (impact factor: 16.642; cited by: 3)
- Agrawal, A., et al. “Genomewide Association Study Identifies a Novel Locus for Cannabis Dependence.” Mol Psychiatry, vol.23, no.5, 2018, pp. 1293-1302 (impact factor: 13.204; cited by: 5)
- Russo, E.B. “Taming THC: Potential Cannabis Synergy and Phytocannabinoid-Terpenoid Entourage Effects.” Br J Pharmacol, vo.163, no.7, 2011, pp. 1344-1364 (impact factor: 6.81; cited by: 563)
- Singh, B.K., “Natural Terpenes Prevent Mitochondrial Dysfunction, Oxidative Stress and Release of Apoptotic Proteins during Nimesulide-hepatotoxicity in Rats.” PLoS One, vol.7, no.4, 2012, pp. e34200 (impact factor: 2.766; cited by: 49)
- Sindhi, V., et al. “Potential Applications of Antioxidants – A Review.” Journal of Pharmacy Research, vol.7, no.9, 2013, pp. 828-835 (impact factor: 2.97; cited by: 94)
- Rosen, G.M., et al. “Mechanism of Free-radical Generation by Nitric Oxide Synthase.” Chem Rev, vol.102, no.4, 2002, pp. 1191-1200 (impact factor: 52.613; cited by: 136)
- Lo, A., et al. “Carnosol, an Antioxidant in Rosemary, Suppresses Inducible Nitric Oxide Synthase through Down-regulating Nuclear Factor-κB in Mouse Macrophages.” Carcinogenesis, vol.23, no.6, 2002, pp. 983-991 (impact factor: 5.334; cited by: 283)
- Gallily, R., et al. “The Anti-Inflammatory Properties of Terpenoids from Cannabis.” Cannabis Cannabinoid Res, vol.3, no.1, 2018, pp. 282-290 (impact factor: N/A; cited by: 1)
- Rufino, A.T., et al. “Evaluation of the Anti-inflammatory, Anti-catabolic and Pro-anabolic Effects of E-caryophyllene, Myrcene and Limonene in a Cell Model of Osteoarthritis.” Eur J Pharmacol, vol.750, 2015, pp. 141-50 (impact factor: 2.896; cited by: 50)
