The Sedative and Anxiolytic Activities of Cedrol and Virginian Cedarwood Essential Oil

Cedrol

Cedrol is a tricyclic sesquiterpene alcohol commonly occurring in the essential oils of conifer trees, especially those belonging to the Cupressus and Juniperus genera. It occurs in essential oil of Juniperus virginiana (Virginian, red or Eastern red cedarwood) (Figure 1) at proportions of approximately 24-32% (ter Heide et al, 1988; Kitchens et al, 1971). The compound presents minimal risk in terms of skin irritancy, allergenicity and toxicity (Tisserand & Young, 2014).

     Figure 1. Virginian cedarwood (Juniperus virginiana)

Cedrol has exhibited in vitro antimicrobial activity against Gram-positive bacteria and yeast, and cytotoxic activity against human lung, liver and oral cancer cells (Su et al, 2012). The compound was also shown to contribute to the potentially beneficial effects of the methanol extract of Juniperus chinenesis on Alzheimer’s disease, specifically through inhibiting the enzymes acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) (Jung et al, 2015). 

In a Korean study, cedrol stimulated the production of the dermal extracellular matrix (including collagen and elastin) that supports skin structure and prevents wrinkle formation (Jin et al, 2012). It has also been shown through in vivo research to promote hair growth (Zhang et al, 2016; Zhang et al, 2018). 

Sedative and anxiolytic effects

In an in vivo study that analyzed the cardiovascular and respiratory effects of inhaling fumes of cedrol extracted from Virginian cedarwood, the compound was shown to significantly decrease heart rate, systolic and diastolic blood pressure, and respiratory rates. Spectral analysis of heart rate variability and the ratio of low to high frequency components indicated that cedrol induces an increase in parasympathetic activity and a reduction in sympathetic activity, pointing to a relaxant effect. (Dayawansa et al, 2003).

Further in vivo research found that, when inhaled, cedrol acts on the peripheral nervous system innervating the lower respiratory tract, indicating potential efficacy in the treatment of hypertension and sleep apnoea, in which elevated sympathetic activity plays a role (Umeno et al, 2007). A similar study found that cedrol increases hippocampal cerebral blood flow (Hori et al, 2012), abnormalities of which are associated with cognitive impairment and depression (Suzuki et al, 2016).

In a trial involving people residing in three different countries (Norway, Thailand and Japan), the sedative effect of inhaling cedrol was shown to be independent of living environment (Yada et al, 2007), while another study revealed that the effect does not depend on the olfactory system (Kagawa et al, 2003).

Recent studies have demonstrated that cedrol has an anxiolytic activity through increasing the level of serotonin and decreasing the level of dopamine and norepinephrine in the brain, in a manner that acts on the hypothalamic–pituitary–adrenal (HPA) axis. Anxiety was reduced without significant suppression of locomotor activity (Zhang et al, 2019; Zhang et al, 2020).

Virginian cedarwood essential oil 

The sedative and anxiolytic effects of cedrol are mirrored in research studies involving essential oil of Virginian cedarwood (Juniperus virginiana). 

Exposure to the odor of the essential oil significantly shortened non-rapid eye movement (NREM) sleep latency in humans, indicating a sedative effect (Sano et al, 1998).

In a study utilising oil of Juniperus virginiana containing α-cedrene (28.11%), β-cedrene (7.81%), cedrol (24.58%) and thujopsene (17.71%), the essential oil at 400–800 m per kg demonstrated an anxiolytic effect in mice, acting through through the serotonergic and dopaminergic pathways (Zhang et al, 2018).

Cedarwood essential oils are classified by Peter Holmes (2019) as “sesquiterpene dominant relaxants with sweet-woody fragrance… restorative as well as relaxant to the nervous system, and therefore perfect for treating chronic combined Weak-Tense terrain”. A chronically weak-tense terrain is often present in cases of generalized anxiety disorder and anxious depression, specifically where lethargy and low mood combine with mental-emotional agitation.

Based on the evidence discussed, Virginian cedarwood essential oil, administered through inhalation, is highly indicated in such cases, particularly in light of the sedative, anxiolytic and cognition-enhancing activities of its constituent cedrol. 

Moreover, Virginian cedar, in terms of the tree’s sustainability, is a IUCN plant of Least Concern (Farion, 2013) – and so the essential oil is an ideal analog for oil of Atlas cedarwood (Cedrus atlantica), which as a species is classified as Endangered (Ablard, 2017).


Guest Post By: 

Gabriel Mojay LicAc,CertEd,FIFPA

References

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Dayawansa S, Umeno K, Takakura H, Hori E, Tabuchi E, Nagashima Y, Oosu H, Yada Y, Suzuki T, Ono T, Nishijo H (2003). Autonomic responses during inhalation of natural fragrance of cedrol in humans. Auton Neurosci. 2003 Oct 31;108(1-2):79-86.

Farjon A (2013). Juniperus virginiana. The IUCN Red List of Threatened Species 2013: e.T42257A2967510. https://dx.doi.org/10.2305/IUCN.UK.2013-1.RLTS.T42257A2967510.en. Downloaded on 27 April 2020. 

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Jin MH, Park SG, Hwang YL, Lee MH, Jeong NJ, Roh SS, Lee Y, Kim CD, Lee JH (2012). Cedrol enhances extracellular matrix production in dermal fibroblasts in a MAPK-dependent manner. Ann Dermatol. 2012 Feb;24(1):16-21.

Jung HJ, Jung HA, Min BS, Choi JS (2015). Anticholinesterase and β-site amyloid precursor protein cleaving enzyme 1 inhibitory compounds from the heartwood of Juniperus chinensis. Chem Pharm Bull (Tokyo). 2015;63(11):955-60.

Kagawa D, Jokura H, Ochiai R, Tokimitsu I, Tsubone H (2003). The sedative effects and mechanism of action of cedrol inhalation with behavioral pharmacological evaluation. Planta Med. 2003 Jul;69(7):637-41. 

Kitchens GC, Dorsky J, Kaiser R (1971). Cedarwood oil and its derivatives. Givaudanian (1), 3-10.

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Su YC, Hsu KP, Wang EI, Ho CL (2012). Composition, anticancer, and antimicrobial activities in vitro of the heartwood essential oil of Cunninghamia lanceolata var. konishii from Taiwan. Nat Prod Commun. 2012 Sep;7(9):1245-7.

Suzuki H, Matsumoto Y, Ota H, Sugimura K, Takahashi J, Ito K, Miyata S, Furukawa K, Arai H, Fukumoto Y, Taki Y, Shimokawa H (2016). Hippocampal blood flow abnormality associated with depressive symptoms and cognitive impairment in patients with chronic heart failure. Circ J. 2016 Jul 25;80(8):1773-80.

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Umeno K, Hori E, Tsubota M, Shojaku H, Miwa T, Nagashima Y, Yada Y, Suzuki T, Ono T, Nishijo H (2008). Effects of direct cedrol inhalation into the lower airway on autonomic nervous activity in totally laryngectomized subjects. Br J Clin Pharmacol. 2008 Feb;65(2):188-96.

Yada Y, Sadachi H, Nagashima Y, Suzuki T (2007). Overseas survey of the effect of cedrol on the autonomic nervous system in three countries. J Physiol Anthropol. 2007 May;26(3):349-54.

Zhang K, Yao L (2018). The anxiolytic effect of Juniperus virginiana L. essential oil and determination of its active constituents. Physiol Behav. 2018 May 15;189:50-58.

Zhang K, Yao L (2019). Anxiolytic effect of cedrol on behavior and brain neurotransmitter levels of female mice. Biol Pharm Bull. 2019 Sep 1;42(9):1575-1580.

Zhang K, Lu J, Yao L (2020). Involvement of the dopamine D1 receptor system in the anxiolytic effect of cedrol in the elevated plus maze and light-dark box tests. J Pharmacol Sci. 2020 Jan;142(1):26-33.

Zhang Y, Han L, Chen SS, Guan J, Qu FZ, Zhao YQ (2016). Hair growth promoting activity of cedrol isolated from the leaves of Platycladus orientalis. Biomed Pharmacother. 2016 Oct;83:641-647.

Zhang Y, Wang JW, Qu FZ, Zhang YM, Su GY, Zhao YQ (2018). Hair growth promotion effect of cedrol cream and its dermatopharmacokinetics. RSC Adv, 2018, 8, 42170.


Photo credit: By uwdigitalcollections - Juniperus virginiana, Red cedarUploaded by Magnus Manske, CC BY 2.0, https://commons.wikimedia.org/w/index.php?curid=21103619

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