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How Terpenes Work with CBD to Help Relieve Anxiety

Did you know that the distinct smell of a cannabis strain can be connected to its ability to relieve anxiety? Certain aromatic compounds called terpenes play a significant role in enhancing the soothing and grounding effects of your bud. Find out which terpenes to look for when you need the most powerful relief for stress and anxiety.

Cannabis research is becoming more and more mainstream, including research on CBD, a major compound found in the plant, which suggests it may help relieve anxiety1 2. In the video below, Sundial Chief Medical Officer, Dr. Jamie Cox, talks about the protocols he used for prescribing CBD to ease anxiety in his clinical practice.

 

 

THC is responsible for causing euphoria, or the characteristic “high” of cannabis. It can be helpful for pain, nausea and sleep disturbance, but as Dr. Cox mentions in the video above, he doesn’t recommend it for patients with anxiety. CBD, on the other hand, could be the anti-anxiety star of medical cannabis.

Most of the research on CBD has been done using the isolated compound, rather than whole cannabis3 4. However, CBD is just one of the hundreds of compounds present in cannabis that may increase its ability to soothe stress and anxiety.

Cannabis contains several known cannabinoids, such as CBD, CBG, CBN and THCA, as well as other classes of compounds known as terpenes and flavonoids. All of these chemicals are thought to work together in a process called “the entourage effect” where they create more enhanced effects together than any single compound does on its own. When it comes to relieving anxiety, several terpenes in cannabis have shown therapeutic promise and seem to bolster the anti-anxiety effects of CBD.

What Are Terpenes?

Terpenes are a large and diverse class of essential oils produced by many plant species and some insects5. In cannabis, terpenes and cannabinoids are created in trichomes, crystalline glands which occur densely on female flowers and sparsely on other aerial parts of the plant6.

Over 200 terpenoid compounds have been identified in cannabis7. These essential oils are responsible for the characteristic odours and tastes of different strains of cannabis. Terpene profiles vary considerably from strain to strain8.

 

Which Terpenes Can Help Relieve Anxiety?

The terpenes beta-caryophyllene, alpha-pinene, linalool, limonene, nerolidol and alpha-bisabolol have all shown promise when it comes to relieving anxiety9. Most of the scientific evidence to date has been gathered in animals, with limited research on humans.

beta-Caryophyllene (BCP) is unique because it is the only terpene known to work through the endocannabinoid receptor 2 (CB2)10. CB2 is one of the body’s major endocannabinoid receptors (CB1 being the other). CB2 that is thought to help regulate our immune responses, inflammatory reactions and emotions, particularly in anxiety and depressive-related disorders11 12 13.

 

Learn More: A Medical Introduction to the Endocannabinoid System

 

Recent studies in animals show that beta-caryophyllene affects behaviours connected to anxiety and depression, which researchers believe are controlled through CB214.

alpha-Pinene (α-PN) has been shown in animal studies to have anti-anxiety effects when inhaled, most likely through binding to a different receptor in the body, the GABAA receptor15.

Linalool (LNL) is the active ingredient in lavender and has shown anti-anxiety effects in animals16. The anti-anxiety properties of linalool were also suggested in a small human study; inhaling linalool affected a region of the brain involved in anxiety17.

The terpene Limonene (LIM) is common to lemon and citrus fruits. In early studies using mice, administering citrus essential oil (containing limonene) seemed to provide anti-anxiety properties, potentially by acting through the serotonin receptor, 5-HT1A18.

The terpenes nerolidol (NOH) and alpha-bisabolol (BISA) have also been shown to exert anti-anxiety effects in animals19 20.

Recently, a group of 442 medical cannabis patients were surveyed about the effectiveness of their cannabis strain in treating anxiety. The strains that were rated as the most effective had high levels of nerolidol, beta-caryophyllene and limonene21.

How to Choose an Anti-Anxiety Cannabis Strain

When choosing a cannabis strain, the ideal compound profile will offer anti-anxiety properties without an intoxicating high, since this can increase anxiety or cause paranoia. Patients usually look for strains that are rich in CBD as well as beta-caryophyllene, alpha-pinene, linalool, limonene, nerolidol, alpha-bisabolol or some combination of these.

Based on current research, it seems that anxiety-relieving terpenes have different ways of working with CBD. Compounds such as beta-caryophyllene, alpha-pinene, linalool and alpha-bisabolol may have an additive effect with CBD, meaning their own anti-anxiety effects add together with those of CBD. These terpenes appear to work through different mechanisms than CBD22 23 24 25. Other terpenes such as limonene seem to act synergistically (in co-operation) with CBD; they seem to provide their anti-anxiety effects through the same serotonin signalling pathway as CBD26 27 28 29 30.

Summary

In addition to CBD, cannabis also contains other active compounds called terpenes. Several of these terpenes have shown promise for treating anxiety in animal studies and anecdotal reports, although this remains to be confirmed in robust human trials.

Terpene content varies considerably between strains, so when choosing a strain to relieve anxiety, look for strains high in CBD as well as the terpenes beta-caryophyllene, alpha-pinene, linalool, limonene, nerolidol or alpha-bisabolol.

  

References

[1] Linares IM, Zuardi AW, Pereira LC, et al. Cannabidiol presents an inverted U-shaped dose-response curve in a simulated public speaking test Brazilian Journal of Psychiatry. 2019;41:9-14.

[2] Shannon S, Lewis N, Lee HS, Hughes S. Cannabidiol in Anxiety and Sleep: A Large Case Series. The Permanente journal. 2019;23:18-041.

[3] Linares IM, Zuardi AW, Pereira LC, et al. Cannabidiol presents an inverted U-shaped dose-response curve in a simulated public speaking test Brazilian Journal of Psychiatry. 2019;41:9-14.

[4] Shannon S, Lewis N, Lee HS, Hughes S. Cannabidiol in Anxiety and Sleep: A Large Case Series. The Permanente journal. 2019;23:18-041.

[5] Gershenzon J, Dudareva N. The function of terpene natural products in the natural world. Nature Chemical Biology. 2007;3:408.

[6] Andre CM, Hausman JF, Guerriero G. Cannabis sativa: The Plant of the Thousand and One Molecules. Frontiers in Plant Sciences. 2016;7:19.

[7] Russo EB. Taming THC: potential cannabis synergy and phytocannabinoid-terpenoid entourage effects. Br J Pharmacol. 2011;163(7):1344-1364.

[8] Russo EB, Marcu J. Cannabis Pharmacology: The Usual Suspects and a Few Promising Leads. Advances in Pharmacology. 2017;80:67-134.

[9] Nuutinen T. Medicinal properties of terpenes found in Cannabis sativa and Humulus lupulus. European Journal of Medicinal Chemistry. 2018;157:198-228.

[10] Gertsch J, Leonti M, Raduner S, et al. Beta-caryophyllene is a dietary cannabinoid. Proceedings of the National Academy of Sciences. 2008;105(26):9099-9104.

[11] Piomelli D. The endocannabinoid system: a drug discovery perspective. Current Opinion in Investigational Drugs. 2005;6(7):672-679.

[12] Mackie K. Cannabinoid receptors as therapeutic targets. Annual Review of Pharmacology and Toxicology. 2006;46:101-122.

[13] Marco EM, Garcia-Gutierrez MS, Bermudez-Silva FJ, et al. Endocannabinoid system and psychiatry: in search of a neurobiological basis for detrimental and potential therapeutic effects. Frontiers in Behavioural Neuroscience. 2011;5:63.

[14] Bahi A, Al Mansouri S, Al Memari E, Al Ameri M, Nurulain SM, Ojha S. β-Caryophyllene, a CB2 receptor agonist produces multiple behavioral changes relevant to anxiety and depression in mice. Physiology & Behavior. 2014;135:119-124.

[15] Nuutinen T. Medicinal properties of terpenes found in Cannabis sativa and Humulus lupulus. European Journal of Medicinal Chemistry. 2018;157:198-228.

[16] Linck VM, da Silva AL, Figueiro M, Caramao EB, Moreno PR, Elisabetsky E. Effects of inhaled Linalool in anxiety, social interaction and aggressive behavior in mice. Phytomedicine. 2010;17(8-9):679-683.

[17] Ota M, Sato N, Sone D, Ogura J, Kunugi H. (-)-Linalool influence on the cerebral blood flow in healthy male volunteers revealed by three-dimensional pseudo-continuous arterial spin labeling. Indian J Psychiatry. 2017;59(2):225-227.

[18] Russo EB. Taming THC: potential cannabis synergy and phytocannabinoid-terpenoid entourage effects. Br J Pharmacol. 2011;163(7):1344-1364.

[19] Goel RK, Kaur D, Pahwa P. Assessment of anxiolytic effect of nerolidol in mice. Indian Journal of Pharmacology. 2016;48(4):450-452.

[20] Tabari MA, Tehrani MAB. Evidence for the involvement of the GABAergic, but not serotonergic transmission in the anxiolytic-like effect of bisabolol in the mouse elevated plus maze. Naunyn Schmiedebergs Arch Pharmacol. 2017;390(10):1041-1046.

[21] Kamal BS, Kamal F, Lantela DE. Cannabis and the Anxiety of Fragmentation—A Systems Approach for Finding an Anxiolytic Cannabis Chemotype. Frontiers in Neuroscience. 2018;12(730).

[22] Nuutinen T. Medicinal properties of terpenes found in Cannabis sativa and Humulus lupulus. European Journal of Medicinal Chemistry. 2018;157:198-228.

[23] Bahi A, Al Mansouri S, Al Memari E, Al Ameri M, Nurulain SM, Ojha S. β-Caryophyllene, a CB2 receptor agonist produces multiple behavioral changes relevant to anxiety and depression in mice. Physiology & Behavior. 2014;135:119-124.

[24] Ota M, Sato N, Sone D, Ogura J, Kunugi H. (-)-Linalool influence on the cerebral blood flow in healthy male volunteers revealed by three-dimensional pseudo-continuous arterial spin labeling. Indian J Psychiatry. 2017;59(2):225-227.

[25] Tabari MA, Tehrani MAB. Evidence for the involvement of the GABAergic, but not serotonergic transmission in the anxiolytic-like effect of bisabolol in the mouse elevated plus maze. Naunyn Schmiedebergs Arch Pharmacol. 2017;390(10):1041-1046.

[26] Russo EB. Taming THC: potential cannabis synergy and phytocannabinoid-terpenoid entourage effects. Br J Pharmacol. 2011;163(7):1344-1364.

[27] Gomes FV, Resstel LB, Guimaraes FS. The anxiolytic-like effects of cannabidiol injected into the bed nucleus of the stria terminalis are mediated by 5-HT1A receptors. Psychopharmacology (Berl). 2011;213(2-3):465-473.

[28] Soares Vde P, Campos AC, Bortoli VC, Zangrossi H, Jr., Guimaraes FS, Zuardi AW. Intra-dorsal periaqueductal gray administration of cannabidiol blocks panic-like response by activating 5-HT1A receptors. Behav Brain Res. 2010;213(2):225-229.

[29] Resstel LB, Tavares RF, Lisboa SF, Joca SR, Correa FM, Guimaraes FS. 5-HT1A receptors are involved in the cannabidiol-induced attenuation of behavioural and cardiovascular responses to acute restraint stress in rats. Br J Pharmacol. 2009;156(1):181-188.

[30] Campos AC, Guimaraes FS. Involvement of 5HT1A receptors in the anxiolytic-like effects of cannabidiol injected into the dorsolateral periaqueductal gray of rats. Psychopharmacology (Berl). 2008;199(2):223-230.