Horticulture

Limonene’s Effects on Anxiety and Depression

Limonene, a monoterpene, is considered to be the second most widely distributed terpene in nature [1], behind the mighty α-pinene [2], and is formed naturally from a pinene precursor. It’s obviously common to citrus fruits, but also to juniper, herbs like dill, mint, and sage, celery, marigolds, and spices like cardamom and nutmeg.

The scent of citrus can be invigorating and uplifting, which makes sense since limonene possesses anxiolytic (anti-anxiety) activity. [3-5, 7-9] One study found that an essential oil extracted from lemon increased serotonin levels in the prefrontal cortex region of the brain, and increased dopamine levels in the hippocampus. [5] The prefrontal cortex is involved in behaviors such as planning, decision-making, and personality. Dopamine is mostly associated with mediating behavior based on rewards. Drugs that make you feel good, like opioids, act on dopamine receptors and increase its release. Dopamine also influences decisions based on relative reward or aversion.

Serotonin is a neurotransmitter associated with happiness and feelings of wellbeing. Of our millions of brain cells, a majority are either directly or indirectly affected by serotonin. These cells include those that play roles in our psychology, such as social behavior, sexual desire or mood, and processes like sleep or memory. In fact, common SSRI (selective serotonin reuptake inhibitor) therapies like Prozac® or Zoloft® are based on the relationship between serotonin levels and depression.

A study on limonene’s efficacy as an anti-depressant investigated whether simply breathing a fragrant citrus vapor would have an effect on patients hospitalized for depression. [6] Nine of twelve patients reduced their dosages of antidepressants following limonene inhalation. Reduction and normalization of both urinary cortisol and dopamine were measured compared to those patients who only dosed with antidepressant medications. Although the sample size was very small, researchers concluded that citrus treatment normalized neuroendocrine hormone levels and immune function more effectively than the available pharmaceutical antidepressants. They pointed out that their findings support the notion that depression is associated with a lack of homeostasis (balance), especially within the immune and neuroendocrine systems.

These findings, while limited in scope, are interesting, given the known roles that the endocannabinoid system plays. Our bodies produce endocannabinoids and cannabis produces phytocannabinoids that help pull our physiological processes back from spiraling to far outside of normal ranges. And in this study, a citrus fragrance made from terpenes including limonene (quite common in cannabis) helped regulate levels of some biochemicals, thereby providing the feeling of “normalcy”. Thus, this cannabis terpene is yet another molecule that helps us “even out”, from migrating too far out of whack.

Limonene’s “balancing” properties may result from its effect on the sympathetic nervous system, which activates the “flight or fight” response, including modulating heart rate and blood pressure. [5] Thus, it was postulated that limonene may affect physiological responses to stress. Based on the anti-stress properties lemon oil exhibited on mice, limonene’s presence in the essential oil extracted from Cannabis was hypothesized as the causative agent of stress-reduction reported by participants who had inhaled this oil. [7] Interestingly, as discussed in the above source in terms of terpinolene, limonene increased beta waves in test subjects when the oil was inhaled, although this brain activity is associated with states of alertness or anxiety. [8]

What’s more, a recent study that evaluated different cannabis cultivars for their anxiety-invoking (anxiogenic) and anxiety-relieving (anxiolytic) properties found that Kush varieties were ranked as most effective for treating anxiety. [9] These plants contained elevated levels of beta-caryophyllene, trans-nerolidol, and limonene.

So where possible, and especially if you’re feeling anxious or rather moody, stop and smell the flowers, since the nose knows what’s good for you.

References:

[1] Noma, Y. and Asakawa, Y. “3.19 – Biotransformation of Monoterpenoids”, Comprehensive Natural Products II, Chemistry and Biology, 2010, Volume 3: 669-801. [journal impact factor = N/A; cited by N/A] [2] Noma Y, Asakawa Y. “Biotransformation of monoterpenoids by microorganisms, insects, and mammals”, In: Baser KHC, Buchbauer G (eds). Handbook of Essential Oils: Science, Technology, and Applications, 2010, CRC Press: Boca Raton, FL, pp. 585–736. [journal impact factor = N/A; cited by 17] [3] Carvalho-Freitas M. and Costa M. “Anxiolytic and sedative effects of extracts and essential oil from Citrus aurantium L.”, Biol Pharm Bull, 2002, Volume 25: 1629–1633. [journal impact factor = 1.694; cited by 146] [4] Pultrini A. et al. “Effects of the essential oil from Citrus aurantium L. in experimental anxiety models in mice”, Life Sci, 2006, Volume 78: Pages 1720–1725. [journal impact factor = ; cited by ] [5] Komiya, M. et al. “Lemon oil vapor causes an anti-stress effect via modulating the 5-HT and DA activities in mice,” Behavioural Brain Research, 2006, Volume 172(2): Pages 240–249.  [journal impact factor = 3.002; cited by 173] [6] Komori, T. et al. “Effects of citrus fragrance on immune function and depressive states,” Neuroimmunomodulation, 1995, Volume 2(3): Pages 174-80. [journal impact factor = 2.238; cited by 131] [7] Gullini, N. et al., “Cannabis Essential Oil: A Preliminary Study for the Evaluation of the Brain Effects”, Evidence-Based Complementary and Alternative Medicine, 2018, Volume 2018, Article ID 1709182, 11 pages. [journal impact factor = 2.064; cited by 3] [8] Sowndhararajan, K. et al. “Effect of olfactory stimulation of isomeric aroma compounds, (+)-limonene and terpinolene on human electroencephalographic activity”, European Journal of Integrative Medicine, 2015, Volume 7(6): Pages 561-566. [journal impact factor = 0.769; cited by 7] [9] Kamal, B. et al. “Cannabis and the Anxiety of Fragmentation—A Systems Approach for Finding an Anxiolytic Cannabis Chemotype”, Frontiers in Neuroscience, 2018, Volume 12: Article 730. [journal impact factor = 3.566; cited by N/A]

About the author

Jason S. Lupoi, Ph.D.

Jason S. Lupoi, Ph.D.

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