Terpenes and Anxiety

How they exert their anxiolytic effects

Substantial evidence has demonstrated the potent anxiolytic effects of the cannabis plant. [1] While much of the literature has focused on the most famous cannabinoids–cannabidiol (CBD) and tetrahydrocannabinol (THC)–additional compounds within the cannabis plant also contribute to these effects.

Terpenes, the powerful substances that give different cannabis chemovars their signature scents, possess an array of beneficial medicinal properties. Clocking in at approximately 10% of overall trichrome content, these compounds have been increasingly studied for their therapeutic potential for many different symptoms and conditions—one of which being the treatment of anxiety. [2]

A seminal review paper authored by Ethan Russo, MD surveyed the literature on terpenes and how they work with phytocannabinoids to produce “entourage effects,” as first described by Raphael Mechoulam, PhD and colleagues. [3] This synergism explains the divergent effects seen from use of single cannabinoid compounds compared to full-spectrum cannabis flower or extract. [1]

These differences are likely due to the pharmacological properties of terpenes. They interact with a wide array of ion channels, neurotransmitter receptors, and enzymes, potentially “boosting” the effects of phytocannabinoids by allowing cannabinoids to influence a greater number of targets in the brain and body. [1]

As for anxiety, pre-clinical studies have indicated that the terpenes linalool, limonene, myrcene, and β-caryophyllene, among others, possess anti-anxiolytic properties. [2] In fact, since terpenes can be found in plants other than cannabis, these results have been confirmed by studies of non-cannabis terpenes. For example, lavender, which contains linalool, is known for its calming and sedating effects. [4]

Terpenes, as independent compounds and as large contributors to the cannabis entourage effect, exert their anxiolytic effects in different ways. For example, linalool induces sedative effects by acting on glutamate and GABA receptors. [5] Glutamate receptors normally work to increase excitation in the brain, while GABA induces inhibitory effects (like the ones experiences after imbibing alcoholic beverages). Both GABA and glutamate have been implicated in the etiology of anxiety. [4]

β-Caryophyllene, however, regulates anxiety through cannabinoid receptors. This terpene, also found in black pepper, is a full agonist at the CB₂ receptor, meaning that when bound and present, it completely turns the receptor “on”. A pre-clinical study demonstrated the effects of β-caryophyllene on anxiety-like behaviors. Additionally, administration of a CB₂ receptor antagonist, which blocks the effects of the receptor, reversed the anxiolytic effects. This indicates that β-caryophyllene mediates anxiety through the CB₂ receptor. [6]

But, as described, these terpenes exhibit far greater effects when used with phytocannabinoids. Studies have shown that linalool works synergistically with CBD, and β-caryophyllene with THC (possibly for anxiety, but definitely shown for inflammation). [1]

Of course additional research on terpenes and how they interact with cannabinoids is necessary to obtain a better understanding of their mechanism of action and therapeutic potential. However, in choosing a product for anxiety or another medical condition or symptom, it’s important to consider the entourage effect and the differences you might experience when using a single cannabinoid compound compared to full-spectrum cannabis.

The differences between the two are largely driven by the presence or absence of terpenes, which contain a variety of benefits—some of which we are just beginning to scratch the surface on.

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References

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: 596)
2. Kamal, B.S., et al., “Cannabis and the Anxiety of Fragmentation—A Systems Approach for Finding an Anxiolytic Cannabis Chemotype.” Front Neurosci, vol.12, no. 730, 2018, pp. 1-14. (impact factor: 3.877; cited by: 2)
3. Ben-Sabbat, S., et al. “An entourage effect: inactive endogenous fatty acid glycerol esters enhance 2-arachidonoyl-glycerol cannabinoid activity.”
4. Saki, K., et al., “The Effect of Most Important Medicinal Plants on Two Important Psychiatric Disorders (Anxiety and Depression): A Review.” Asian Pac J Trop Med, vol.1, suppl.1, 2014, pp. S34-42. (impact factor: 1.634; cited by: 137)
5. Nunes, D.S., et al. (2010). Psychopharmacology of essential oils. In: Baser KHC, Buchbauer G (eds). Handbook of Essential Oils: Science, Technology, and Applications. CRC Press: Boca Raton, FL, pp. 297–314. (impact factor: N/A; cited by: 551)
6. Bahi, A., et al., “β-Caryophyllene, A CB2 Receptor Agonist Produces Multiple Behavioral Changes Relevant to Anxiety and Depression in Mice.” Physiol Behav. vol.135, 2014, pp. 119-124. (impact factor: 3.033; cited by: 111)