PTSD, Olfaction, and Essential Oil Orange

Human and animal studies have shown that Citrus sinensis (#orange #essentialoil), has physiological and psychological effects that result in the decrease of fear, stress, and anxiety.

Posttraumatic Stress Disorder (PTSD) is a mental health disorder that can develop after a traumatic event. In Diagnostic and Statistical Manual of Mental Disorders: DSM-5, the American Psychiatric

According to the National Center for PTSD, 8 million people in a given year will be affected by symptoms associated with PTSD. (1)

Association defines the experience of a traumatic event as "exposure to actual or threatened death, serious injury, or sexual violence (2)". In the United States, "about 7 or 8 out of every 100 people (or 7-8% of the population) will have PTSD at some point in their lives.(3) Most people think of military personnel as the only group of the general public that are largely affected by PTSD due to their experiences during deployments in war-torn countries, but PTSD can affect anyone given the criteria.

PTSD Sufferers

#PTSD sufferers experience a range of symptoms such as chronic #insomnia associated with #nightmares, dissociative #flashbacks, #agoraphobia, #avoidance, #depression, emotional numbness, and severe #anxiety, to name a few. Environmental stressors such as persons, places, and certain smells and scents can abruptly trigger an emotional state for sufferers by reminding them of an aversive past incident.(4) Early studies focusing on the #olfactory system show "... that when a novel odor is paired with an emotional event, hedonic perception of that odor is altered in accord with the associated emotion.(5)" However, just as certain trauma-related smells and scents trigger fear-related memories for a PTSD sufferer, discovering appealing aromas that bring pleasant memories and calming emotions is certainly possible, and possible through aromatherapy.

#Aromatherapy is the use of concentrated plant extracts known as essential oils that are taken from herbs, flowers, and other plant parts to treat diseases. Citrus sinensis (Orange) is an essential oil that is steam distilled from the orange peel. It comes from the #monoterpene family and is considered a high note which means that its volatility, i.e., evaporation rate, is high. Proponents of aromatherapy claim the medicinal effects of orange essential oil help a client holistically, a view that is still met with skeptism by the western medical establishment. d-limonene is a primary chemical constituent in orange essential oil and has been attributed to being an antidepressant in massage (6) whereas the inhalation of d-limonene has an anxiolytic action (7).

Olfaction

#Olfaction is one of the five human senses and is simply the sense of smell. Yet, in its simplicity a dynamic, complex system exists. The olfactory system processes an odor or odorant molecule in the following way. An odorant molecule enters and travels up the nasal cavity. There the odorant molecule encounters the olfactory epithelium or membrane which holds tiny cilia that act as receptors. The odorant molecule binds to specific cilia on the olfactory epithelium that activate olfactory receptor cells. These cells in turn belong to G protein-coupled receptors (#GPCR). GPCR stimulates the formation of #cAMP (cyclic AMP), and this messenger molecule activates an ion channel that allows signal activation of the odorant receptor cell (7). From there, the odorant receptor cell is sent to its associated glomerulus. The electrical action response transverses into proteins and is sent from the #glomerulus down through the olfactory bulb. The chemical proteins arrive at the amygdala and use an alternative mechanism to arrive at the #orbitalfrontal cortex. Eventually, the action response reaches the hippocampus. "Unlike other senses, the olfactory neuroanatomy is intertwined via extensive reciprocal axonal connections, with primary emotion areas including the #amygdala, #hippocampus, and orbitalfrontal cortex (8)." Encoding thereby takes place in each region of the brain and associates the odorant molecule with a memory and an emotion.

The olfactory process amazingly assigns hedonic meaning to odor memory. Studies have shown that what is pleasant to some people incites something unpleasant in others. (9) In their research and discussion of three medical case reports, Eric Vermetten and J. D. Bremner stated that,

Odor memory is independent of other types of memory and is long lasting, with a resistance to decay over long intervals. This view, known now as "Proustian" view, also holds that odor memory is excellent for odors associated with significant autobiographical experiences. The relationship between olfaction and autobiographical memories appears to be stronger when the experiences are more significant and emotionally charged.(10)

For PTSD sufferers trauma-related odor memory can be detrimental and disabling as a particular smell can bring back aversive memories. '

Olfactory flashbacks can be disabling phenomena due to intrusive nature of memories. A wide variety of cues are mentioned as precipitants of flashback phenomena, varying from experiences with little and transient emotional disturbance to emotional responses that last longer and that evoke symptoms like anxiety, nervousness, nausea, and guilt. These symptoms can be mild but in some cases can be accompanied by dramatic fear and avoidance behavior.(11)

Further studies have shown as well that emotion-olfaction interaction can evoke negative mood states and turn innocuous odors aversive. (12)(13)(14)

In a 2015 research article, authors Filomene G. Morrison et al. found increasing evidence that "[f]or those who live with post-traumatic stress disorder (PTSD), the sense of smell could one day play a prominent role in treatment" (15). In their research mice were subjected to olfactory fear-conditioning thus exhibiting enhanced fear-potentiated startle (FPS) and freezing specific to the conditioned odor stimulus. Morrison et al. added that

Reversing the behavioral and neuroanatomical effects of such emotion learning is important for our understanding of disorders such as posttraumatic stress disorder (PTSD), in which exposure-based psychotherapy is widely used for treatment. Notably, extinction training in rodent fear-conditioning models closely parallels many aspects of exposure-based psychotherapy in humans where exposure to nonreinforced presentations of the previously acquired conditioned stimulus (CS) reduces acquired fear responses such as freezing to the CS. (16)

Here, extinction training and exposure therapy involve the formation of new memories related to the fear cues and contexts; that is , in PTSD, the reminders of the traumatic event. (17). By looking at the structural changes in the brain Morrison et al. believed that fear-conditioning trauma in the external environment can be encoded on a genetic level pertaining to the olfactory sensory neurons on the mass olfactory epithelium (18). It can then be said that the connection between odors and memories is a powerful one, especially those from the distant past, charged with emotional significance due to major anatomical connections existing between brain structures such as the limbic system which is involved in emotion and memory. This point further demonstrates that the application of aromatherapy via the olfactory system can be an ideal alternative treatment for PTSD sufferers on cellular and neuroanatomical levels.

Orange Essential Oil

Human studies have shown that the medicinal uses of orange essential oil, when applied, extend from treating microbial activity to reducing pain to relieving stomach aches. (19) In regards to the central nervous system, Lehrner et al. (20) and Lehrner et al. (21) determined through their research that ambient odor of essential oil in dental office environments greatly reduces fear and anxiety among patients waiting for a dental procedure. Lerhner et al. (22) went further by comparing the outcome of orange essential oil to that of lavender. The application of lavender, a well-known and well-researched essential oil, has positive effects in dealing with a variety of mental health conditions such as anxiety, for example, when combined externally through massage (23) or internally administered (24). Lehrner et al. (25) determined that orange essential oil had no less of an effect than lavender. For orange essential oil to have a comparable effect as lavender gave further proof that it could be used for anxiety relief.

In another study Jafazrzadeh et al. (26) investigated the effect of aromatherapy using orange essential oil with children before and after their dental appointments. The researchers looked at the difference in means of salivary cortisol and pulse rate which indicates the level of stress and anxiety that a child feels upon entering a dental appointment. The researchers concluded that "... the use of aromatherapy with natural essential oil of orange could reduce salivary cortisol and pulse rate due to child anxiety state. (27)

Rashidi-FAkari et al. (28) did a similary study but in a medical setting about the effect of aromatherapy by orange essential oil on anxiety of women who were in labor. The investigation reported that the intervention group receiving orange essential oil overcame their anxiety during labor and that orange essential oil could be useful in childbirth units to help women who are experiencing stress in labor.

Another investigation (29) involved a simulated anxiogenic scenario to which 40 healthy male adults were subjected. Orange essential oil was used as a test aroma with 2.5, 5, and 10 drops; tea tree (Melaleuca alternifolia) essential oil (2.5 drops) was the control aroma; and water was the non-aromatic control with 2.5 drops. The subjects were measured by psychologic parameters such as state anxiety, subjective tension, tranquilization, and physiological parameters such as heart rate and gastrocnemius electromyogram. Again, we continue seeing results showing that

the anxiolytic properties of sweet orange essential oil through the lack of a significant increase in state anxiety and tension, and the lack of a significant decrease in tranquility, presented by the individuals exposed to the aroma. (30)

In a similar study, orange essential oil demonstrated anxiolytic activity in at least one of the tests and, at the highest dose (400 microliter), it presented significant effects in both animal models (31). These results suggested that "an acute anxiolytic activity of sweet orange essence, giving some scientific support to its use as a tranquilizer by aromatherapists" (32).

In their 2017 animal research, Moshfegh et al. (33) studied whether orange essential oil as a natural method could provide relief for some symptoms of PTSD. Moshfegh et al. developed an experiment that involved exposure to orange essential oil and Pavlovian fear conditioning on mice. The mice were trained "to associate a cue with a non-harmful stimulus so that they responded fearfully to a non-harmful stimulus in a way that models some symptoms of human PTSD (34)." One way of exhibiting fear is that mice will freeze whan an audible tone is rung. Moshfegh et al. subjected the mice to longer exposure times to orange essential oil as the test control; water was used as the non-aromatic control. The results revealed

the stress hormone levels as well as inflammatory immune cell phenotypes were no different between the control and two treatment groups, indicating that the observed differences in fear response were not caused by changes in the stress response or by potential inflammatory stress.(35)

Furthermore, the study revealed that mice exposed to orange essential oil showed a significant reduction in freezing behavior and stopped freezing much earlier than those mice inhaling non-aromatic water. The alteration of the mice's behavior in spite of the fear-conditioned stimulus provided further support of orange essential oil having a therapeutic property of tranquilization and anti-anxiety relieving effects.

Research related to PTSD and essential oils in general is virtually non-existent. But the above research can be shown that it can relate to some of the symptoms a person suffering with PTSD might experience. Furthermore, the research results are indicative that orange essential oil can be used as an effective alternative treatment for those symptoms such as fear, stress, and anxiety.

Bibliography

(1) American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders: DSM-5. 5th Edition. Arlington, VA: American Psychiatric Association, 2013.

(2) Author unknown, National Center for PTSD, U.S. Department of Veterans Affairs (2020) "How Common is PTSD in Adults?" https://www.ptsd.va.gov/understand/common/common_adults.asp cited as of December, 2020.

(3) ibid.

(4) Vermetten, E. and Bremner, J.D. (2003) "Olfaction as a Traumatic Reminder in Posttraumatic Stress Disorder: CAse Reports and Review. J Clin Psychiatry: 64:00-00.

(5) Herz, R. S. (2005) "Odor-associative Learning and Emotion: Effects on Perception and Behavior." Chemical Senses Vol 30 (Suppl 1): i250-i251.

(6) Hongratanaworakit, T. and Buchbauer, G. (2007) "Autonomic and emotional responses after transdermal absorption of sweet orange oil in humans: placebo controlled trial. International Journal of Essential Oil Therapeutics 1, 29-34.

(7) Lima, N.G., de Souza, D.P., Pimenta, F.C., Alves, M.F. de Souza, F.S. (2012) "Anxiolytic-like activity and GC-MS analysis of (R)-(+)-limonene fragrance, a natural compound found in foods and plants." Pharmacology, Biochemistry, and Behavior 103, 450-454.

(8) Krusemark, E. A., Novak, L. R., Gitelman, D. R., and Wen, L. (2013) "When the Sense of Smell Meets Emotion: Anxiety-State-Dependent Olfactory." Processing and Neural Circuitry Adaptation, Journal of Neuroscience, 33 (39) 15324-15332.

(9) Herz, ibid.

(10) Vermetten, E. and Bremner, J. D., ibid.

(11) ibid.

(12) Herz, ibid.

(13) Krusemark, ibid.

(14) Wen, Li. (2014) "Learning to smell danger: acquired associative representation of threat in the olfactory cortex." Frontiers in Behavioral Neuroscience, Volume B, Article 98: 1-8.

(15) Morrison, F. G. Dias, B.G., Ressler, K.J. (2015) "Extinction reverses olfactory fear-conditioned increases in neuron number and glomerular size. Proceedings of the National Academy of Sciences 112(41): 1-6.

(16) ibid.

(17) Dunlop, B. W. and Rothbaum, B.O. (2019) "Medication-Assisted Psychotherapy for PTSD". PTSD Research Quarterly: Advancing Science and Promoting Understanding of Traumatic Stress. Volume 30, No. 3, pp. 1-2.

(18) Morrison et al., ibid.

(19) Seladi-Schulman, J. (2019) "The Benefits of Orange Essential Oil and How to Use." https://www.healthline.com/health/orange-essential-oil-uses cited as of December 16, 2020.

(20) Lehrner, J., Eckersberger, C., Walla, P., Potsch, G., Deecke, L. (2000) "Ambient odor of orange in a dental office reduces anxiety and improves in female patients." Physiology & Behavior, 71, pp. 83-86.

(21) Lehrner, J. Marwinski, Lehr, S., Johren, P., Deecke, L. (2005) "Ambient odor of orange and lavender reduce anxiety and improve mood in a dental office." Physiology & Behavior 86, pp. 92-95.

(22) Lerhner, J. et al., (2005) ibid.

(23) Cooke, B., and Edzard, E., (2000) "Aromatherapy: A Systematic Review". British Journal of General Practice, 2000, 50, 493-496.

(24) Kasper, S., Gastpar, M., Muller, W. E., Volz, H-P, Moller, H-J, Schlafke, S., and Dienel, A., (2014) "Lavender oil preparation Silexan is effective in generalized anxiety disorder - a randomized double-blind comparison to placebo and paroxetine. International Journal of Neuropsychopharmacology (2014), 17, 859-869.

(25) Lerhner, J. et al., (2005) ibid.

(26) Jafarzadeh, M., Arman, S., and Pour, F.F. (2013) "Effect of aromatherapy with orange essential oil on salivary cortisol and pulse rate in children during dental treatment: A randomized controlled clinical trial." Advanced Biomedical Research 2: 10. Published online 2013 March 6 at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3732892/ cited on December 16, 2020.

(27) ibid.

(28) Rashidi-Fakari, F., Tabatabaeichehr, M., and Mortazavi, H. (2015) "The effect of aromatherapy by essential oil of orange on anxiety during labor: A randomized clinical trial." Iran J Nurs Midwifery Res. Novermber-December, pp. 661-664.

(29) Goes, T. C., Dias Antunes, F., Barreto Alves, P., and Teixeira-Silva, F., (2012) "Effect of Sweet Orange Aroma on Experimental Anxiety in Humans." The Journal of Alternative and Complementary Medicine. Volume 18, Number 8, pp. 798-804.

(30) ibid.

(31) Faturi, C.B., Leite, J.R., Alves, P.B., Canton, A.C. (2010) "Anxiolytic-like effect of sweet orange aroma in Wistar rats." Prog Neuropsychopharmacol Biol Psychiatry 2010 May 30 34(4) pp. 605-609.

(32) ibid.

(33) Moshfegh, C., et al., (2016) "Effects of Essential Oil on Fear Memory and the Immune Response; A Potential Alternative Therapy for Post-Traumatic Stress Disorder (PTSD)." The FASEB Journal, 30: Supplement 1238.5.

(34) ibid.

(35) ibid.